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Sample records for lymphocyte th1 cytokine

  1. Effect of interleukin-33 on Th1/Th2 cytokine ratio in peripheral lymphocytes in asthmatic mice

    Institute of Scientific and Technical Information of China (English)

    He Xinliang; Wu Wei; Lu Yan; Guo Yali; Hu Chaoliang; Huang Yuyun; Xu Yuzu

    2014-01-01

    Background Allergic asthma is a chronic airway inflammatory disease partly characterised by high concentration of T help 2 (Th2) cytokines in bronchoalveolar lavage fluid (BALF).There is no report on the relation of peripherally circulating blood lymphocytes and asthma.We explored the balance of Th2/Th1 cytokines in asthmatic mice.Exogenous recombinant interleukin (IL) 33 acted on mudne peripheral circulating blood lymphocytes,IL-5 cytokine was selected for assessing Th2 cytokines and interferon-gamma (IFN-y) for Th1 cytokines.Methods Female specific pathogen free BABL/c mice were sensitised by intraperitoneal injection of 20 μg of ovalbumin emulsified in 1 mg of aluminium hydroxide gel in a total volume of 200 μl,and challenged for 30 minutes in 7 consecutive days with an aerosol of 2 g ovalbumin in 100 ml of PBS.Then we collected BALF and isolated lymphocytes from the peripheral blood.The lymphocytes were divided into two groups:asthmatic group and normal group.Th1/Th2 cytokines was detected by enzyme-linked immunosorbent assay (ELISA) kits.Results In the asthma group,we found numerous eosinophils and lymphocytes on the glass slides.We then confirmed that the optimal concentration of IL-33 was 10 ng/ml and time of IL-33 stimulating lymphocytes was 24 hours.In the asthma group,the production of IL-5 was significantly increased over normal group after stimulation with IL-33 (P <0.05)and the production of IFNy was supressed from IL-33 stimulated lymphocytes (P <0.05).Conclusion IL-33 acts on lymphocytes of peripheral blood increasing secretion of Th2 cytokines and inhibiting secretion of Th1 cytokines.

  2. A novel lectin from Artocarpus lingnanensis induces proliferation and Th1/Th2 cytokine secretion through CD45 signaling pathway in human T lymphocytes.

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    Cui, Bo; Li, Lu; Zeng, Qiyan; Lin, Faquan; Yin, Lijun; Liao, Liejun; Huang, Min; Wang, Jingping

    2017-04-01

    Lectins are carbohydrate-binding proteins and have been used for purification and characterization of glycoproteins. In this study, a novel 58.9-kDa tetrameric lectin from Artocarpus lingnanensis seeds was purified, characterized, and its mitogenic potential was evaluated. The hemagglutination inhibition assay indicated that Artocarpus lingnanensis lectin (ALL) showed specificity toward galactose. ALL was effectively purified in a single-step using affinity chromatography on a galactose-Sepharose column. ALL showed pH optima between 5.0 and 9.0, and optimal temperature between 20 and 40 °C. ALL triggered proliferation and activation of human T lymphocytes (e.g., CD4(+) T lymphocytes). Flow cytometry and laser scanning confocal microscopy revealed binding of ALL to T cells and colocalized with CD45. Affinity chromatography and Western blot suggested that CD45 isolated from human T cell membrane fraction may be the major receptor of ALL. CD45 blocking antibody attenuated the binding and proliferation of T cells induced by ALL. CD45-PTPase inhibitor dephostatin reduced ALL-induced T cells proliferation and expression of CD25 and pZAP-70. Furthermore, secretion of ALL-induced Th1/Th2 cytokines was blocked with dephostatin. Also, dephostatin inhibited phosphorylation of ALL-mediated activation of ERK and p38MAPK. This study demonstrates the involvement of CD45-mediated signaling in ALL-induced T lymphocyte proliferation and Th1/Th2 cytokine secretion through activation of p38 and ERK.

  3. [EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

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    Zabrodskii, P F; Maslyakov, V V; Gromov, M S

    2016-01-01

    It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

  4. [Effects of different doses of L-arginine on the serum levels of helper T lymphocyte 1 (Th1)/Th2 cytokines in severely burned patients].

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    Yan, Hong; Peng, Xi; Wang, Pei; Huang, Yue-sheng; Wang, Shi-liang

    2009-10-01

    To investigate the effects of L-arginine in different doses on the serum levels of helper T lymphocyte1 (Th1)/Th2 cytokines in severely burned patients. Twenty-nine severely burned patients, with total burn surface area from 50% to 80%TBSA, hospitalized within 20 hours after burn, were randomly divided into control group (10 cases, fed with 5% glucose saline 500 mL), L-arginine 200 mg group (10 cases, fed with 5% glucose saline 500 mL + 200 mg/kg L-arginine), L-arginine 400 mg group (9 cases, fed with 5% glucose saline 500 mL + 400 mg/kg L-arginine). All patients received enteral feeding through nasointestinal tube, started within 22 hours after burn. Fasting venous blood of all patients was harvested on post burn day (PBD) 1 (before enteral feeding), 3, 5, and 7 to determine serum contents of TNF-alpha, IL-1beta, TGF-beta(1) and IL-4 by radio-immunity method and enzyme-linked immunosorbent assay. Serum contents of TNF-alpha and IL-1beta of patients in all groups increased rapidly after burn, and although contents of TNF-alpha (318 +/- 57) ng/mL and IL-1beta (218 +/- 47) pg/mL of patients in L-arginine 200 mg group peaked on PBD 5, they were still significantly lower than those of patients in control group [(389 +/- 34) ng/mL, (272 +/- 40) pg/mL, P 0.05). Serum contents of TGF-beta(1) and IL-4 of patients in each group increased slowly after burn, and content of TGF-beta(1) (110 +/- 16) pg/mL of patients in L-arginine 200 mg group was significantly higher than that of patients in control group [(83 +/- 20) pg/mL, P 0.05). Compared with the dosage of 400 mg/kg L-arginine, the 200 mg/kg dose is more effective in reducing the release of Th1 cytokines and increasing Th2 cytokines production, hence maintaining Th1/Th2 cytokine ratio to produce better immune opsonization during the infection phase of severe burn.

  5. Oral Administration of Bovine Milk from Cows Hyperimmunized with Intestinal Bacterin Stimulates Lamina Propria T Lymphocytes to Produce Th1-Biased Cytokines in Mice

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    Yuanyuan Wang

    2014-03-01

    Full Text Available The goal of this study was to examine the effects of oral administration of bovine milk from cows hyperimmunized with a proprietary bacterin (immune milk “Sustaina” on mucosal immunity in the intestine of adult mice. C57BL/6 mice were orally given immune or control milk for two weeks, and then lymphocyte population and the cytokine production in lamina propria of colon in normal mice and mice induced colitis by dextran sulphate sodium (DSS were detected. We found that the levels of IFN-γ and IL-10 increased, but the levels of IL-17A and IL-4, decreased in lamina propria of colon in immune milk-fed mice as compared with those in control milk-fed mice. Interestingly, oral administration of immune milk partially improved the acute colitis induced by DSS. The levels of TNF-α and IFN-γ increased, but IL-6, IL-17A and IL-4 decreased in lamina propria (LP of colon in immune milk-fed mice with DSS-induced colitis. Our results suggest that immune milk may stimulate CD4+ T cells to polarize towards a Th1 type response, but contrarily suppress Th17 and Th2 cells responses in large intestinal LP of mice. The results indicate that this kind of immune milk has is able to promote the maintainance of intestinal homeostasis and enhance protection against infection, and could alleviate the symptoms of acute colitis in mice.

  6. Th1/Th2 Cytokines in Psoriasis

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    Z Jadali

    2007-08-01

    Full Text Available Background: The aim of this study was to determine the Th1 and Th2 serum cytokines, in patients with psoriasis and to com¬pare their cytokine levels with those of normal control subjects. Methods: Serum levels of Interferon-gamma (IFN-γ, Interleukin-2 (IL-2, Interleukin-4 (IL-4, and Interleukin-10 (IL-10 were measured by enzyme linked immunosorbent assay in 40 patients with psoriasis and in 40 normal controls. Results: Compared with control subjects, patients with psoriasis had elevated levels of IFN-γ and IL-2 (P<0.001. In addi¬tion a positive correlation was found between the levels of IFN-γ, IL-2 and disease severity. Conclusion: Th1 secreting inflammatory cytokines may contribute to the pathogenesis of psoriasis.

  7. Effects of salbutamol aerosol combined with magnesium sulfate on T-lymphocyte subgroup and Th1/Th2 cytokines of pediatric asthma

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    Diao, Min; Min, Jie; Guo, Fei; Zhang, Chong-Lin

    2017-01-01

    The aim of the study was to analyze the effects of the intravenous infusion of salbutamol aerosol combined with magnesium sulfate in the treatment of pediatric asthma and the subsequent effects on the levels of T-lymphocyte subgroups and Th1/Th2 cytokines. A total of 86 patients with pediatric asthma, first diagnosed and treated at the Xuzhou Children's Hospital, were continuously selected and randomly divided into an observation group of 44 cases and control group of 42 cases. The patients in the control group were treated with budesonide atomization inhalation, while the children in the observation group were treated with intravenous infusion of salbutamol aerosol combined with magnesium sulfate. The therapeutic effects in the groups were compared. After treatment, the levels of serum CD3+ and CD8+ decreased when compared to before treatment; the levels of CD4+ and CD4+/CD8+ also increased, but the observation group had more significant improvement. Differences were statistically significant (P<0.05). After treatment, the levels of serum interleukin-2 (IL-2) and interferon-γ (IFN-γ) increased when compared to before, while levels of IL-4 and IL-6 decreased, and the observation group had more significant improvement. The differences were statistically significant (P<0.05). After treatment, the levels of VT, t-PTEF/t-E, MTIF/MTEF and TEF75/PTEF increased when compared to before; the observation group had more significant improvement. The differences were statistically significant (P<0.05). The effective rate and degree of treatment for the observation group were significantly higher than those of the control group and differences were statistically significant (P<0.05). The intravenous infusion of salbutamol aerosol combined with magnesium sulfate in the treatment of pediatric asthma can significantly improve therapeutic effects and lung functions, improve immune functions and relieve inflammatory reactions. Therefore, it indicates better clinical application and

  8. Th1 cytokine-based immunotherapy for cancer

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    Hong-Mei Xu

    2014-01-01

    Cytokine-based immunotherapy is executed by harnessing cytokines to activate the immune system to suppress tumors. Th1-type cytokines including IL-1, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor are potent stimulators of Th1 differentiation and Th1-based antitumor response. Many preclinical studies demonstrated the antitumor effects of Th1 cytokines but their clinical efficacy is limited. Multiple factors influence the efficacy of immunotherapy for tumors. For instance immunosuppressive cells in the tumor microenvironment can produce inhibitory cytokines which suppress antitumor immune response. Most studies on cytokine immunotherapy focused on how to boost Th1 response; many studies combined cytokine-based therapy with other treatments to reverse immunosuppression in tumor microenvironment. In addition, cytokines have pleiotropic functions and some cytokines show paradoxical activities under different settings. Better understanding the physiological and pathological functions of cytokines helps clinicians to design Th1-based cancer therapy in clinical practice.

  9. EXPRESSION AND SWITCHING OF TH 1/TH2 TYPE CYTOKINES GENE IN HUMAN GLIOMAS

    Institute of Scientific and Technical Information of China (English)

    Yong-sheng Hu; Xin-gang Li; Qing-lin Zhang; Dong-hai Wang; Song-feng Gong

    2005-01-01

    Objective To study the expression and switching of Th1/Th2 cytokines gene in hman gliomas and its effects on occurring and developing of human gliomas.Methods Interleukin(IL)-2 and intefferon-γ represent Th1 type cytokines. IL-4, IL-6, IL-10, and IL-13 represent Th2 type cytokines. The gene expressions of Th1/Th2 cytokines in human glioma cells, glioma infiltrating lymphocytes,and glioma cell lines were detected by reverse transcription polymerase chain reaction (RT-PCR). The biological activity of cytokines in the supematant of glioma cell lines was assayed by enzyme-linked immunosorbent assay (ELISA)method.Results The total positive rates of Th1 and Th2 type cytokines gene in human glioma cells were 14.77% and 75%. The total positive rates of Thl and Th2 type cytokines gene in glioma infiltrating lymphocytes were 22.73% and 68.17%. There was obviously predominant expression of Th2 type cytokines in human glioma tissues, glioma infiltrating lymphocytes, and glioma cell lines. There was no unbalanced expression of Th1/Th2 cytokines in normal brain tissues.Conclusion There is a predominant expression of Th2 type cytokines in human glioma cells. The switching of Th1/Th2 cytokines gene may play an important role in the occurring and developing of human gliomas.

  10. Intracellular cytokine production by Th1/Th2 lymphocytes and monocytes of children with symptomatic transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD)

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    Kowalczyk, D; Baran, J; Webster, A D B; Zembala, M

    2002-01-01

    Intracellular expression of several cytokines was assessed in lymphocytes and monocytes of children with transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD). THI was characterized by an increased frequency of CD3+/CD4+ lymphocytes expressing tumour necrosis factor α (TNF-α), TNF-β and interleukin 10 (IL-10), while in SIgAD elevated numbers of these cells containing TNF-α and interferon γ (IFN-γ) were observed. No changes in the number of CD4+ T cells expressing IL-4 in both diseases were noted. The proportion of CD33+ monocytes containing TNF-α both in THI and SIgAD was unchanged. The secretion of IL-12 by peripheral blood mononuclear cells (PBMCs) of patients with THI and SIgAD was significantly elevated and associated with an increased frequency of IL-12 expressing monocytes in THI but not in SIgAD. IL-18 secretion was slightly, but not significantly, elevated in both diseases. Intracellular Th1 and Th2 type cytokines within CD3+/CD4+ lymphocytes were also determined in the normal blood donors that showed high or low production of IgG and IgA in vitro. In low producers of IgG an increased proportion of CD3+/CD4+ cells expressing TNF-α and IFN-γ was found, while in low IgA responders only elevated TNF-α positive CD3+/CD4+ cells were observed. These results suggest that THI and SIgAD may represent diseases with an excessive Th1 type response that is associated with an up-regulation of IL-12 secretion and, at least in THI, elevated numbers of monocytes expressing intracellular IL-12. Up-regulation of IL-12 may be the essential factor in the patomechanism(s) of these diseases as already described in common variable immunodeficiency (CVID). PMID:11966768

  11. Th1/Th2 cytokine production and reception features in Graves' disease

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    T V Saprina

    2012-06-01

    Full Text Available Cytokines and their receptors belong to a significant role in the initiation and the subsequent course and outcome of autoimmune thyroid disease. Interleukin-2 (IL-2, interleukin-4 (IL-4 and tumor necrosis factor-alpha (TNF-α-cytokines, which have a multifaceted impact on the various stages of the immune response: the development of inflammatory response, cell proliferation, antibody and acute phase proteins synthesis. Pre-existing pattern of development of autoimmune thyroiditis (Hashimoto's thyroiditis and Graves' disease (GD as a state with two opposite positions of the predominant profile of Th1/Th2-lymphocyte activation. The study evaluated the cytokine production by Th1- and Th2-lymphocytes in patients with GD, assessment of lymphocyte receptor system and identified lymphocytes subpopulation in patients with BG, and the impact on the functional state of thyroid gland. It was shown that the immunoregulatory cytokines as Th1(IL2- and Th2(IL-4-helper lymphocytes are involved in the immune mechanism of BG. The level of IL-2, IL4, and TNF-α, and the number complementary lymphocyte receptors were not significantly changed in euthyroid or hyperthyroid GD patient. Nevertheless, there are strong correla! tions between production of immunoregulatory cytokines (IL-2, IL-4 with the functional state of the thyroid gland and increase of its volume in GD patient, what confirms the “functional synergies” of these cytokines in autoimmune inflammation in the GD.

  12. Effect of Malnutrition on the Expression of Cytokines Involved in Th1 Cell Differentiation

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    González-Torres, Cristina; González-Martínez, Haydeé; Miliar, Angel; Nájera, Oralia; Graniel, Jaime; Firo, Verónica; Alvarez, Catalina; Bonilla, Edmundo; Rodríguez, Leonor

    2013-01-01

    Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections. PMID:23429441

  13. Effect of Malnutrition on the Expression of Cytokines Involved in Th1 Cell Differentiation

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    Leonor Rodríguez

    2013-02-01

    Full Text Available Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response and the production of cytokines related to the immunological cellular response (Th1 cytokines. We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines. In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21 are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections.

  14. Effect of malnutrition on the expression of cytokines involved in Th1 cell differentiation.

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    González-Torres, Cristina; González-Martínez, Haydeé; Miliar, Angel; Nájera, Oralia; Graniel, Jaime; Firo, Verónica; Alvarez, Catalina; Bonilla, Edmundo; Rodríguez, Leonor

    2013-02-19

    Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections.

  15. Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway.

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    Mao, Mao; Qian, Yanning; Sun, Jie

    2016-04-01

    To investigate the effect of morphine on T helper lymphocyte differentiation and PI3K/AKT pathway mechanism, CD4+ lymphocytes were treated by phorbol-myristate-acetate (25 ng/ml) (PMA) plus ionomycin (1 μg/ml) in the presence of various concentrations of morphine (25, 50, 100, 200 ng/ml) for 4 h. Th1 and Th2 subsets, supernatant cytokines, and PI3K, AKT, and protein kinase C-theta (PKC-θ) levels were detected. The Th1 cell percentage, Th1-derived cytokines, and ratio of Th1/Th2 decreased in the presence of morphine in a concentration-dependent manner. However, Th2 cell percentage kept stable after morphine treatment. The phosphorylation of PI3K and AKT decreased, but the phosphorylation of PKC-θ did not change in the presence of morphine. The decreased percentage of Th1 cells and ratio of Th1/Th2 was recovered by naloxone concentration-dependently. Morphine can inhibit the differentiation of Th1 lymphocytes and decrease the ratio of Th1/Th2 via the pathway of PI3K/AKT. The effect can be inhibited by naloxone.

  16. Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.

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    Zhang, Shouxin; Liu, Xiaoyan; Sun, Chengming; Yang, Jun; Wang, Lihong; Liu, Jie; Gong, Lei; Jing, Yanyan

    2016-04-01

    This study aims to investigate the protective effect of apigenin on the development of experimental autoimmune myocarditis (EAM) and the underlying mechanisms. An EAM model was induced in BALB/c mice by the injection of porcine cardiac myosin. Apigenin was orally administered from day 1 to 21. The severity of myocarditis was assessed by determination of heart weight/body weight ratio (HW/BW) and histopathological evaluation. Echocardiography was conducted to evaluate the cardiac function and heart structure. Antigen-specific T cell proliferation responses to cardiac myosin were evaluated by the lymphocyte proliferation assay. ELISA was used to determine serum levels of type 1 helper (Th1) and Th2 cytokines. Apigenin treatment significantly decreased HW/BW. Histopathologic analysis showed that the infiltration of inflammatory cells was reduced significantly by apigenin treatment. Meanwhile, apigenin administration effectively ameliorated autoimmune myocarditis-induced cardiac hypertrophy and cardiac dysfunction as well as inhibited lymphocyte proliferation in mice immunized with myosin. Furthermore, Th1 cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) were significantly downregulated, while Th2 cytokines IL-4 and IL-10 were markedly upregulated. The results indicated that apigenin can alleviate EAM due to its immunomodulatory reactions in modification of helper T cell balance.

  17. Dietary glutamine supplementation modulates Th1/Th2 cytokine and interleukin-6 expressions in septic mice.

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    Yeh, Chiu Li; Hsu, Chun-Sun; Yeh, Sung-Ling; Chen, Wei-Jao

    2005-09-01

    Glutamine (Gln) has been demonstrated to have benefit in the modulation of systemic immunity in sepsis. However, the effects of Gln on local immunity and intra-lymphocyte cytokine expression have not been investigated in mice with gut-derived sepsis. This study evaluated the influence of a Gln-enriched diet on interleukin (IL)-6 expression in organs and Th1/Th2 type cytokine production within lymphocytes in septic mice. Male ICR mice were assigned to control and Gln groups. The control group was fed a semi-purified diet, while in the Gln group, Gln replaced part of the casein. After feeding the respective diets for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP). Mice were sacrificed at 0, 6, 12 and 24h after CLP and their organs were harvested for further analysis. Results showed that IL-6 levels in the liver were decreased, whereas levels were increased in the lungs, kidneys and intestines with the progression of sepsis in both groups. Also, intra-lymphocyte interferon (IFN)-gamma expression decreased and IL-4 expression increased during sepsis. Compared to the control group, the Gln group had higher levels of IL-6 in the liver and lower levels in other organs at various time points. Lymphocyte IFN-gamma expression in the Gln group was higher, and IL-4 levels were lower than those of the control group after CLP. These results suggest that Gln supplementation decreased IL-6 production in non-hepatic organs, while reducing intra-lymphocyte IL-4 and enhancing IFN-gamma expressions. This change may reverse the Th2 type response to a more-balanced Th1/Th2 response during sepsis.

  18. Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty

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    Finnegan Alison

    2008-02-01

    Full Text Available Abstract Background All prostheses with metallic components release metal debris that can potentially activate the immune system. However, implant-related metal hyper-reactivity has not been well characterized. In this study, we hypothesized that adaptive immunity reaction(s, particularly T-helper type 1 (Th1 responses, will be dominant in any metal-reactivity responses of patients with total joint replacements (TJAs. We tested this hypothesis by evaluating lymphocyte reactivity to metal "ions" in subjects with and without total hip replacements, using proliferation assays and cytokine analysis. Methods Lymphocytes from young healthy individuals without an implant or a history of metal allergy (Group 1: n = 8 were used to assess lymphocyte responses to metal challenge agents. In addition, individuals (Group 2: n = 15 with well functioning total hip arthroplasties (average Harris Hip Score = 91, average time in-situ 158 months were studied. Age matched controls with no implants were also used for comparison (Group 3, n = 8, 4 male, 4 female average age 70, range 49–80. Group 1 subjects' lymphocyte proliferation response to Aluminum+3, Cobalt+2, Chromium+3, Copper+2, Iron+3, Molybdenum+5, Manganeese+2, Nickel+2, Vanadium+3 and Sodium+2 chloride solutions at a variety of concentrations (0.0, 0.05, 0.1, 0.5, 1.0 and 10.0 mM was studied to establish toxicity thresholds. Mononuclear cells from Group 2 and 3 subjects were challenged with 0.1 mM CrCl3, 0.1 mM NiCl2, 0.1 mM CoCl2 and approx. 0.001 mM titanium and the reactions measured with proliferation assays and cytokine analysis to determine T-cell subtype prominence. Results Primary lymphocytes from patients with well functioning total hip replacements demonstrated a higher incidence and greater magnitude of reactivity to chromium than young healthy controls (p 2 fold stimulation index response, p 10 mM. The differential secretion of signature T-cell subsets' cytokines (Th1 and Th2 lymphocytes

  19. Boswellia carterii extract inhibits TH1 cytokines and promotes TH2 cytokines in vitro.

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    Chevrier, Marc R; Ryan, Abigail E; Lee, David Y-W; Zhongze, Ma; Wu-Yan, Zhang; Via, Charles S

    2005-05-01

    Traditional herbal formulas used to treat inflammatory arthritis in China and India include Boswellia carterii or Boswellia serrata. They both contain boswellic acids (BAs) which have been shown to exhibit anti-inflammatory and antiarthritic properties. This study tests the hypothesis that mixtures of BAs derived from B. carterii have immunomodulatory properties. B. carterii plant resin obtained from China was prepared as an ethanol extract, and the presence of seven BAs was confirmed by column chromatography, high-performance liquid chromatography, and UV laser desorption/ionization tandem mass spectroscopy. The extract was then tested for its ability to alter in vitro production of TH1 cytokines (interleukin-2 [IL-2] and gamma interferon) and TH2 cytokines (IL-4 and IL-10) by murine splenocytes. Delivery of the resin extract using ethanol as a solvent resulted in significant cellular toxicity not seen with the addition of ethanol alone. By contrast, delivery of the resin extract using a sesame oil solvent resulted in a dose-dependent inhibition of TH1 cytokines coupled with a dose-dependent potentiation of TH2 cytokines. These results indicate that a purified mixture of BAs from B. carterii plant resin exhibits carrier-dependent immunomodulatory properties in vitro.

  20. EFFECTS OF STEROID HORMONES UPON TH1/TH2 CYTOKINE PRODUCTION BY CD45RO+ T CELLS

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    A. A. Gutsol

    2013-01-01

    Full Text Available Abstract. The aim of our study was to evaluate effects of steroid hormones upon the imbalance of Th1/Th2 cytokine production (IL-2, IFNγ, IL-4, IL-10 by CD45RO+ activated lymphocytes. In our experiments, we have shown a clear trend of multidirectional influence of steroid hormones upon secretory activity of T-lymphocytes. We have revealed that development of cellular immune responses mediated by type 1 T helper cells is regulated primarily by female sex hormones. Glucocorticoid hormones seem to exert a marked effect upon development of humoral Th2 immune response. For androgens, some controversial results have been obtained.

  1. Predominant expression of Th1-type cytokines in primary hepatic cancer and adjacent liver tissues

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    Fa-Bo Qiu; Li-Qun Wu; Yun Lu; Shun Zhang; Bing-Yuan Zhang

    2007-01-01

    BACKGROUND: Research has revealed a shift towards Th2 in many types of malignant tumor, but the state of Th1/Th2 is not clear in patients with primary hepatic cancer (PHC). This study was designed to determine the expression of Th1-versus Th2-type cytokines in primary hepatic cancer and the adjacent liver tissue in order to provide evidence for treatment of the Th1/Th2 shift. METHODS:Samples were collected from 11 patients with PHC. The gene expression of Th1/Th2 cytokines was detected by reverse transcriptase polymerase chain reaction (RT-PCR) using IFN-γ and IL-2 as Th1-type cytokine genes, and IL-4 and IL-10 as Th2-type cytokine genes. RESULTS: Th1-type cytokines were expressed in 7/11 PHCs and 9/11 adjacent liver tissues, while Th0 type cytokines occurred in 4/11 PHCs and 2/11 adjacent liver tissues. CONCLUSION: Th1-type cytokines are expressed predominantly in primary hepatic cancer and the adjacent liver tissue.

  2. Th1 and Th2 cytokine profile in patients with early onset periodontitis and their healthy siblings

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    Jiřina Bártová

    2000-01-01

    Full Text Available Early onset periodontitis (EOP is a chronic inflammatory periodontal disease with a strong genetic link affecting individuals aged 17 to 25. In the familial studies we tested the hypothesis about the role of Th1 and Th2 cytokines in the pathogenesis of EOP disease. The study involved 6 individuals with EOP disease and their 6 siblings with healthy periodontium. Actinobacillus actinomycetemcomitans (A. a., a bacterium typical for EOP, was detected in all people studied. Th1 and Th2 cytokine production was measured after in vitro stimulation. Peripheral blood mononuclear cells (PBMC were isolated and cultivated for 24 h and 7 days with PWM, A. a. or Escherichia coli. The levels of IL–4, IFN-gamma, IgA, IgG and IgM were measured by ELISA methods. After in vitro stimulation of PBMC, a significantly higher production of IL–4 and significantly lower production of IFN-gamma were found in the group of patients compared with their healthy siblings. The increased level of IL–4 in patients was in good agreement with an increased level of IgM after stimulation of lymphocytes with E. coli. These results support Seymour’s hypothesis according to which patients with progressive disease primarily activate Th2 lymphocytes while non-susceptible individuals activate Th1 lymphocytes.

  3. Differential Ca2+ influx, KCa channel activity, and Ca2+ clearance distinguish Th1 and Th2 lymphocytes.

    Science.gov (United States)

    Fanger, C M; Neben, A L; Cahalan, M D

    2000-02-01

    In Th1 and Th2 lymphocytes, activation begins with identical stimuli but results in the production of different cytokines. The expression of some cytokine genes is differentially induced according to the amplitude and pattern of Ca2+ signaling. Using fura- 2 Ca2+ imaging of murine Th1 and Th2 clones, we observed that the Ca2+ rise elicited following store depletion with thapsigargin is significantly lower in Th2 cells than in Th1 cells. Maximal Ca2+ influx rates and whole-cell Ca2+ currents showed that both Th1 and Th2 cells express indistinguishable Ca2+-release-activated Ca2+ channels. Therefore, we investigated other mechanisms controlling the concentration of intracellular Ca2+, including K+ channels and Ca2+ clearance from the cytosol. Whole-cell recording demonstrated that there is no distinction in the amplitudes of voltage-gated K+ currents in the two cell types. Ca2+-activated K+ (KCa) currents, however, were significantly smaller in Th2 cells than in Th1 cells. Pharmacological equalization of Ca2+-activated K+ currents in the two cell types reduced but did not completely eliminate the difference between Th1 and Th2 Ca2+ responses, suggesting divergence in an additional Ca2+ regulatory mechanism. Therefore, we analyzed Ca2+ clearance from the cytosol of both cell types and found that Th2 cells extrude Ca2+ more quickly than Th1 cells. The combination of a faster Ca2+ clearance mechanism and smaller Ca2+-activated K+ currents in Th2 cells accounts for the lower Ca2+ response of Th2 cells compared with Th1 cells.

  4. Increased Calpain Correlates with Th1 Cytokine Profile in PBMCs from MS Patients

    Science.gov (United States)

    Imam, Sarah A.; Guyton, Mary K.; Haque, Azizul; Vandenbark, Arthur; Tyor, William R.; Ray, Swapan K.; Banik, Naren L.

    2007-01-01

    Multiple sclerosis (MS) is a devastating autoimmune demyelinating disease of the CNS. This study investigated whether expression and activity of the calcium-activated protease calpain correlated with Th1/Th2 dysregulation in MS patients during states of relapse and remission. Calpain expression and activity were significantly increased in peripheral blood mononuclear cells (PBMCs) from MS patients, compared to controls, with the highest expression and activity noted during relapse. Th1 cytokines were highest and Th2 cytokines were lowest in MS patients during relapse. Treatment with calpain inhibitor, calpeptin, decreased Th1 cytokines in PBMCs from MS patients. Calpain inhibitor also reduced degradation of myelin basic protein (MBP) by inhibiting the calpain secreted from MBP-specific T cells. Taken together, these results suggested calpain involvement in Th1/Th2 dysregulation in MS patients. PMID:17765980

  5. Dysregulated cytokine expression by CD4+ T cells from post-septic mice modulates both Th1 and Th2-mediated granulomatous lung inflammation.

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    William F Carson

    Full Text Available Previous epidemiological studies in humans and experimental studies in animals indicate that survivors of severe sepsis exhibit deficiencies in the activation and effector function of immune cells. In particular, CD4+ T lymphocytes can exhibit reduced proliferative capacity and improper cytokine responses following sepsis. To further investigate the cell-intrinsic defects of CD4+ T cells following sepsis, splenic CD4+ T cells from sham surgery and post-septic mice were transferred into lymphopenic mice. These recipient mice were then subjected to both TH1-(purified protein derivative and TH2-(Schistosoma mansoni egg antigen driven models of granulomatous lung inflammation. Post-septic CD4+ T cells mediated smaller TH1 and larger TH2 lung granulomas as compared to mice receiving CD4+ T cells from sham surgery donors. However, cytokine production by lymph node cells in antigen restimulation assays indicated increased pan-specific cytokine expression by post-septic CD4+ T cell recipient mice in both TH1 and TH2 granuloma models. These include increased production of T(H2 cytokines in TH1 inflammation, and increased production of T(H1 cytokines in TH2 inflammation. These results suggest that cell-intrinsic defects in CD4+ T cell effector function can have deleterious effects on inflammatory processes post-sepsis, due to a defect in the proper regulation of TH-specific cytokine expression.

  6. 褐藻胶对小鼠脾淋巴细胞Th1/Th2细胞因子谱影响的体内外研究%Effects of alginate on Th1/Th2 cytokines in vivo and in vitro of mice spleen lymphocytes

    Institute of Scientific and Technical Information of China (English)

    黄琼; 黄俊明; 杨杏芬; 蔡玟; 黄建康; 李志; 李宁; 徐海滨

    2009-01-01

    目的 研究褐藻胶对小鼠脾淋巴细胞Th1/Th2细胞因子谱的影响.方法 体内实验:分别设阴性对照组和两个褐藻胶组(0.50g/kg bw和1.50g/kg bw),每组各5只C57BL/6小鼠,分别经口给予纯净水和褐藻胶.30天后分离脾淋巴细胞,培养48h后取上清采用流式微球分析术(CBA)方法分析白细胞介素(IL-2、IL-4、IL-5)、肿瘤坏死因子(TNF)和干扰素-γ(IFN-γ)水平.体外实验:分离C57BL/6种小鼠脾淋巴细胞,与褐藻胶(25rag/ml和50mg/m1)培养48h后取上清采用CBA方法分析IL-2、IL-4、IL-5、TNF和IFN-γ水平.结果 体内实验:0.5g/kg bw和1.5g/kg bw褐藻胶组IFNγ表达水平明显高于阴性对照组(P<0.01),而IL-2和IL-4表达水平下降(P<0.01,P<0.05).体外实验:25mg/ml和50mg/ml褐藻胶组,TNF、IL-2和IL-4表达均明显高于阴性对照组(P<0.05,P<0.01),50mg/ml褐藻胶组IL5表达水平明显高于阴性对照组(P<0.01).结论 无论是在体内还是体外实验条件下,褐藻胶对小鼠脾淋巴细胞分泌的Th1/Th2细胞因子谱均有影响.

  7. Mangiferin Attenuates Th1/Th2 Cytokine Imbalance in an Ovalbumin-Induced Asthmatic Mouse Model

    Science.gov (United States)

    Hou, Guang-Han; Du, Jun; Huang, Xin; Lu, Yi; Keller, Evan T.; Zhang, Jian; Deng, Jia-Gang

    2014-01-01

    Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway. PMID:24955743

  8. Mangiferin attenuates TH1/TH2 cytokine imbalance in an ovalbumin-induced asthmatic mouse model.

    Directory of Open Access Journals (Sweden)

    Hong-Wei Guo

    Full Text Available Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12 and Th2 cytokines (IL-4, IL-5 and IL-13. Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway.

  9. Lactobacillus Acidophilus Strain L-92 Regulates the Production of Th1 Cytokine as well as Th2 Cytokines

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    Akiko Torii

    2007-01-01

    Conclusions: Oral L-92 administration regulated both Th1 and Th2 cytokine responses, suppressed serum OVA-specific IgE, and induced TGF-β production in PPs. TGF-β is known to be associated with activation of regulatory T (Treg cells. These data suggest that LAB may have immunomodulative effect by Treg cells via TGF-β activity.

  10. Th-1, Th-2 Cytokines Profile among Madurella mycetomatis Eumycetoma Patients.

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    Amre Nasr

    2016-07-01

    Full Text Available Eumycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by certain fungi, the most common being Madurella mycetomatis. The host defence mechanisms against fungi usually range from an early non-specific immune response to activation and induction of specific adaptive immune responses by the production of Th-1 and Th-2 cytokines. The aim of this study is to determine the levels of Th-1 and Th-2 cytokines in patients infected with Madurella mycetomatis, and the association between their levels and disease prognosis. This is a descriptive cross-sectional study conducted at the Mycetoma Research Centre, University of Khartoum, Sudan, where 70 patients with confirmed M. mycetomatis eumycetoma were enrolled; 35 with, and 35 without surgical excision. 70 healthy individuals from mycetoma endemic areas were selected as controls. The levels of serum cytokines were determined by cytometric bead array technique. Significantly higher levels of the Th-1 cytokines (IFN-γ, TNF-α, IL-1β and IL-2 were recorded in patients treated with surgical excision, compared to those treated without surgical excision. In contrast, the Th-2 cytokines (IL-4, IL-5, IL-6 and IL-10 were significantly lower in patients treated with surgical excision compared to those treated without surgical excision. In conclusion, the results of this study suggest that cell-mediated immunity can have a role to play in the pathogenesis of eumycetoma.

  11. Th-1, Th-2 Cytokines Profile among Madurella mycetomatis Eumycetoma Patients.

    Science.gov (United States)

    Nasr, Amre; Abushouk, Amir; Hamza, Anhar; Siddig, Emmanuel; Fahal, Ahmed H

    2016-07-01

    Eumycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by certain fungi, the most common being Madurella mycetomatis. The host defence mechanisms against fungi usually range from an early non-specific immune response to activation and induction of specific adaptive immune responses by the production of Th-1 and Th-2 cytokines. The aim of this study is to determine the levels of Th-1 and Th-2 cytokines in patients infected with Madurella mycetomatis, and the association between their levels and disease prognosis. This is a descriptive cross-sectional study conducted at the Mycetoma Research Centre, University of Khartoum, Sudan, where 70 patients with confirmed M. mycetomatis eumycetoma were enrolled; 35 with, and 35 without surgical excision. 70 healthy individuals from mycetoma endemic areas were selected as controls. The levels of serum cytokines were determined by cytometric bead array technique. Significantly higher levels of the Th-1 cytokines (IFN-γ, TNF-α, IL-1β and IL-2) were recorded in patients treated with surgical excision, compared to those treated without surgical excision. In contrast, the Th-2 cytokines (IL-4, IL-5, IL-6 and IL-10) were significantly lower in patients treated with surgical excision compared to those treated without surgical excision. In conclusion, the results of this study suggest that cell-mediated immunity can have a role to play in the pathogenesis of eumycetoma.

  12. In vitro Th1 cytokine-independent Th2 suppressive effects of bifidobacteria.

    Science.gov (United States)

    Iwabuchi, Noriyuki; Takahashi, Noritoshi; Xiao, Jin-zhong; Miyaji, Kazuhiro; Iwatsuki, Keiji

    2007-01-01

    A comparison between 17 strains of lactic acid bacteria and 15 strains of bifidobacteria indicated that bifidobacteria induced significantly lower levels of interleukin-12 (IL-12) in murine splenic cells. The present study aims to evaluate the effect and mechanism of Bifidobacterium longum BB536, a probiotic strain, in suppressing antigen-induced Th2 immune response in vitro. BB536 suppressed immunoglobulin (Ig) E and IL-4 production by ovalbumin-sensitized splenic cells, but induction of Th1-inducing cytokine production, such as IL-12 and gamma interferon (IFN-gamma) tended to be lower compared with lactic acid bacteria. Neutralization with antibodies to IL-12, IFN-gamma, IL-10 and transforming growth factor beta indicated negative involvement of Th1-inducing cytokines and regulatory cytokines in the suppression of Th2 immune response by BB536, especially when treated at higher doses of BB536 (>10 microg cells/ml). Furthermore, BB536 induced the maturation of immature bone marrow-derived dendritic cells (BM-DCs), and suppressed antigen-induced IL-4 production mediated by BM-DCs. These results suggested that BB536 suppressed Th2 immune responses, partially independent of Th1-inducing cytokines and independent of regulatory cytokines, mediated by antigen-presenting cells such as dendritic cells.

  13. Oxidative stress modulates the cytokine response of differentiated Th17 and Th1 cells.

    Science.gov (United States)

    Abimannan, Thiruvaimozhi; Peroumal, Doureradjou; Parida, Jyoti R; Barik, Prakash K; Padhan, Prasanta; Devadas, Satish

    2016-10-01

    Reactive oxygen species (ROS) signaling is critical in T helper (Th) cell differentiation; however its role in differentiated Th cell functions is unclear. In this study, we investigated the role of oxidative stress on the effector functions of in vitro differentiated mouse Th17 and Th1 cells or CD4(+) T cells from patients with Rheumatoid Arthritis using pro-oxidants plumbagin (PB) and hydrogen peroxide. We found that in mouse Th cells, non-toxic concentration of pro-oxidants inhibited reactivation induced expression of IL-17A in Th17 and IFN-γ in Th1 cells by reducing the expression of their respective TFs, RORγt and T-bet. Interestingly, in both the subsets, PB increased the expression of IL-4 by enhancing reactivation induced ERK1/2 phosphorylation. We further investigated the cytokine modulatory effect of PB on CD4(+) T cells isolated from PBMCs of patients with Rheumatoid Arthritis, a well-known Th17 and or Th1 mediated disease. In human CD4(+) T cells from Rheumatoid Arthritis patients, PB reduced the frequencies of IL-17A(+) (Th17), IFN(-)γ(+) (Th1) and IL-17A(+)/IFN(-)γ(+) (Th17/1) cells and also inhibited the production of pro-inflammatory cytokines TNF-α and IL-6. N-Acetyl Cysteine (NAC) an antioxidant completely reversed PB mediated cytokine modulatory effects in both mouse and human cells indicating a direct role for ROS. Together our data suggest that oxidative microenvironment can alter cytokine response of terminally differentiated cells and thus altering intracellular ROS could be a potential way to target Th17 and Th1 cells in autoimmune disorders.

  14. Multiparameter fluorescence imaging for quantification of TH-1 and TH-2 cytokines at the single-cell level

    Science.gov (United States)

    Fekkar, Hakim; Benbernou, N.; Esnault, S.; Shin, H. C.; Guenounou, Moncef

    1998-04-01

    Immune responses are strongly influenced by the cytokines following antigenic stimulation. Distinct cytokine-producing T cell subsets are well known to play a major role in immune responses and to be differentially regulated during immunological disorders, although the characterization and quantification of the TH-1/TH-2 cytokine pattern in T cells remained not clearly defined. Expression of cytokines by T lymphocytes is a highly balanced process, involving stimulatory and inhibitory intracellular signaling pathways. The aim of this study was (1) to quantify the cytokine expression in T cells at the single cell level using optical imaging, (2) and to analyze the influence of cyclic AMP- dependent signal transduction pathway in the balance between the TH-1 and TH-2 cytokine profile. We attempted to study several cytokines (IL-2, IFN-(gamma) , IL-4, IL-10 and IL-13) in peripheral blood mononuclear cells. Cells were prestimulated in vitro using phytohemagglutinin and phorbol ester for 36h, and then further cultured for 8h in the presence of monensin. Cells were permeabilized and then simple-, double- or triple-labeled with the corresponding specific fluorescent monoclonal antibodies. The cell phenotype was also determined by analyzing the expression of each of CD4, CD8, CD45RO and CD45RA with the cytokine expression. Conventional images of cells were recorded with a Peltier- cooled CCD camera (B/W C5985, Hamamatsu photonics) through an inverted microscope equipped with epi-fluorescence (Diaphot 300, Nikon). Images were digitalized using an acquisition video interface (Oculus TCX Coreco) in 762 by 570 pixels coded in 8 bits (256 gray levels), and analyzed thereafter in an IBM PC computer based on an intel pentium processor with an adequate software (Visilog 4, Noesis). The first image processing step is the extraction of cell areas using an edge detection and a binary thresholding method. In order to reduce the background noise of fluorescence, we performed an opening

  15. CD161 Expression Defines a Th1/Th17 Polyfunctional Subset of Resident Memory T Lymphocytes in Bronchoalveolar Cells.

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    Yolanda Gonzalez

    Full Text Available Alveolar resident memory T cells (T(RM comprise a currently uncharacterized mixture of cell subpopulations. The CD3(+CD161(+ T cell subpopulation resides in the liver, intestine and skin, but it has the capacity for tissue migration; however, the presence of resident CD3(+CD161(+ T cells in the bronchoalveolar space under normal conditions has not been reported. Bronchoalveolar cells (BACs from healthy volunteers were evaluated and found that 8.6% (range 2.5%-21% of these cells were CD3(+ T lymphocytes. Within the CD3(+ population, 4.6% of the cells (2.1-11.3 expressed CD161 on the cell surface, and 74.2% of the CD161(+CD3(+ T cells expressed CD45RO. The number of CD3(+CD161(+ T cells was significantly lower in the bronchoalveolar space than in the blood (4.6% of BACs vs 8.4% of peripheral blood mononuclear cells (PBMCs; P<0.05. We also found that 2.17% of CD4(+ T lymphocytes and 1.52% of CD8(+ T lymphocytes expressed CD161. Twenty-two percent of the alveolar CD3(+CD161(+ T lymphocytes produced cytokines upon stimulation by PMA plus ionomycin, and significantly more interferon gamma (IFN-γ was produced compared with other cytokines (P = 0.05. Most alveolar CD3(+CD161(+ T cells produced interleukin-17 (IL-17 and IFN-γ simultaneously, and the percentage of these cells was significantly higher than the percentage of CD3(+CD161- T cells. Moreover, the percentage of alveolar CD3(+CD161(+ T lymphocytes that produced IFN-γ/IL-17 was significantly higher than those in the peripheral blood (p<0.05. In conclusion, Th1/Th17-CD3(+CD161(+ TRM could contribute to compartment-specific immune responses in the lung.

  16. Schisandrin B inhibits Th1/Th17 differentiation and promotes regulatory T cell expansion in mouse lymphocytes.

    Science.gov (United States)

    Chen, Zhaoyang; Guo, Min; Song, Guohua; Gao, Jiping; Zhang, Yinhong; Jing, Zhijie; Liu, Tianfu; Dong, Chuan

    2016-06-01

    Schisandrin B (Sch-B), the most abundant active ingredient of the fruit of Schisandra chinensis, has been proposed to have antioxidant, anti-tumor and anti-inflammatory effects. The present study was undertaken to investigate the effect of Sch-B on differentiation of T helper cells (Th). Using mouse splenic lymphocytes stimulated with concanavalin A (Con A) in vitro and ex vivo as inflammation models, we found that Sch-B significantly inhibited secretion of Th1 and Th17 related cytokines, such as IFN-γ and IL-17. In addition, we found that Sch-B suppressed the differentiation of naive CD4+ T cells into Th1 and Th17 cells, while promoted their differentiation into the regulatory T cells (Treg) in vitro. We further found that Sch-B suppressed transcription of Th1-related T-box transcription factor, T-bet, and Th17-related transcription factor, retinoid related orphan receptor gamma t (RORγt), while enhanced transcription of Treg-related transcription factor forkhead box protein 3 (Foxp3) in naive CD4+ T cells under Th cell polarization conditions. Furthermore, the effect of Sch-B on the T cell differentiation was abrogated by heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin. Taken together, we conclude that Sch-B can modulate differentiation of naïve CD4+ T cells into specific lineages of effector cells, which may have potential benefits for treatment of autoimmune diseases.

  17. Immunomodulatory activity of xanthohumol: inhibition of T cell proliferation, cell-mediated cytotoxicity and Th1 cytokine production through suppression of NF-κB

    OpenAIRE

    Gao, Xiaohua; Deeb, Dorrah; Liu, Yongbo; DULCHAVSKY, SCOTT A.; Gautam, Subhash C.

    2009-01-01

    Xanthohumol (XN), a prenylated chalcone present in hops (Humulus lupus L.) and beer, exhibits anti-inflammatory, antioxidant and antiproliferative activity, but has not been studied for effects on T cell-mediated immune responses. Here we demonstrate that XN has profound immunosuppressive effects on T cell proliferation, development of IL-2 activated killer (LAK) cells, cytotoxic T lymphocytes (CTLs), and production of Th1 cytokines (IL-2, IFN-γ and TNF-α). The suppression of these cell-media...

  18. Th1/Th2 cytokines in patients with Graves' disease with or without ophthalmopathy.

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    Fatemeh Esfahanian

    2013-06-01

    Full Text Available About 25-50% of Graves' disease (GD patients develop thyroid eye diseases, which is associated with inflammatory process and abnormalities in the levels of several cytokines in orbital tissues in GD.  The aim of this study was to determine the Th1 and Th2 serum cytokines in patients with GD with or without ophthalmopathy.Serum  levels of  cytokines  and  autoantibodies  including Interferon-gamma  (IFN-γ,Interleukin-2 (IL-2, Interleukin-4 (IL-4, Interleukin-10 (IL-10, TSH receptor autoantibody (TRAb, thyroid  peroxidase antibody (TPOAb  and  thyroglobulin antibody(TgAb were measured by enzyme linked immunosorbent assay(ELISA in 34 patients with GD and in 33 normal controls. Patients were also divided in two subgroups: 18 cases with ophthalmopathy and 16 cases without ophthalmopathy. Cytokine and antibody responses were analyzed in both groups.Compared with control subjects, patients with GD  showed elevated levels of IL-2 and IL-10. IFN-γ  levels were lower in patients in comparison to the controls. No significant differences were found  between patients and controls regarding the IL-4. There was no statistically significant  difference  in  cytokine  levels  between  those   with  or   without ophthalmopathy.Quantitative-cytokine  analysis  demonstrated  that  a  combination  of  Th1  and  Th2 cytokines may contribute to the pathogenesis of GD. These results also indicate that IL-10, but not IL-4, is related to the moderate and severe forms of thyroid associated ophthalmophathy.

  19. Heavy metal mediated innate immune responses of the Indian green frog, Euphlyctis hexadactylus (Anura: Ranidae): Cellular profiles and associated Th1 skewed cytokine response.

    Science.gov (United States)

    Jayawardena, Uthpala A; Ratnasooriya, Wanigasekara D; Wickramasinghe, Deepthi D; Udagama, Preethi V

    2016-10-01

    Immune cell and cytokine profiles in relation to metal exposure though much studied in mammals has not been adequately investigated in amphibians, due mainly to lack of suitable reagents for cytokine profiling in non-model species. However, interspecies cross reactivity of cytokines permitted us to assay levels of IFNγ, TNFα, IL6 and IL10in a common anuran, the Indian green frog (Euphlyctis hexadactylus), exposed to heavy metals (Cd, Cr, Cu, Zn and Pb, at ~5ppm each) under field and laboratory settings in Sri Lanka. Enumeration of immune cells in blood and melanomacrophages in the liver, assay of serum and hepatic cytokines, and Th1/Th2 cytokine polarisation were investigated. Immune cell counts indicated overall immunosuppression with decreasing total WBC and splenocyte counts while neutrophil/lymphocyte ratio increased with metal exposure, indicating metal mediated stress. Serum IL6 levels of metal exposed frogs reported the highest (~9360pg/mL) of all cytokines tested. Significantly elevated IFNγ production (Pfrogs. Th1/Th2 cytokine ratio in both serum and liver tissue homogenates was Th1 skewed due to significantly higher production of pro-inflammatory cytokines, IFNγ in serum and TNFα in the liver (P<0.01).Metal mediated aggregations of melanomacrophages in the liver were positively and significantly (P<0.05) correlated with the hepatic expression of TNFα, IL6 and IL10 activity. Overall, Th1 skewed response may well be due to oxidative stress mediated nuclear factor κ-light chain enhancer of activated B cells (NFκB) which enhances the transcription of pro-inflammatory cytokines. Xenobiotic stress has recently imposed an unprecedented level of threat to wildlife, particularly to sensitive species such as amphibians. Therefore, understanding the interactions between physiological stress and related immune responses is fundamental to conserve these environmental sentinels in the face of emerging eco-challenges.

  20. Th1/Th2 cytokines and their genotypes as predictors ofhepatitis B virus related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant typeof primary liver cancer, is one of the most serious lifethreateningmalignancies, worldwide. In majority ofthe cases, HCC develops after prolonged and persistentchronic liver disease. hepatitis B virus (HBV) or HCVinfection is prominent etiological factors, attributing to this condition. It has been well documented that HBV,being the inducer of chronic inflammation, is the maincausative agent in causing HCC, particularly in Asiancountries. The HBV infection leads to a wide range ofclinical symptoms from carrier state to malignancy.Cytokines being immune-modulatory molecules, arethe key mediators in the defense mechanism againstviral infection. In this regard, this review will detail thesubstantial role of key Th1: interleukin 1 (IL-1), IL-2,IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4,IL-10 and non Th1/Th2: IL-6, transforming growthfactor-β1 cytokines genotypes in analyzing the variabilityin the clinical manifestations in an HBV-afflicted individual,which might finally, culminates into HCC. Since cytokineproduction is regulated genetically, the cytokine promoterregion single-nucleotide polymorphisms induced changes,greatly affects the cytokine production, thus resulting intodifferential outcome of immune balance.

  1. Analysis of serum th1/th2 cytokine levels in patients with acute mumps infection

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    Jeevan Malaiyan

    2016-01-01

    Full Text Available Background: The mumps virus is frequently the causative agent of parotitis. There has been no study on serum cytokine levels of acute mumps parotitis except for a few which document cytokine levels in cerebrospinal fluid of mumps meningitis. It is with this notion, our study aimed to find Th1/Th2 cytokine levels from patients with acute mumps parotitis. Materials and Methods: Concentrations of mumps-specific IgM, mumps, measles, rubella-specific IgG antibody, and Th1/Th2 cytokines, namely interferon-g (IFN-g, interleukin-2 (IL-2, IL-4, and IL-10 were measured simultaneously in serum from 74 patients (42 pediatric and 32 adult cases, 40 healthy subjects (20 pediatric and 20 adults and in the supernatant of peripheral blood mononuclear cells stimulated with mumps virus genotype C which served as the positive control. Statistical significance was analyzed between each group by means of Mann-Whitney U-test, Kruskal-Wallis test, and Spearman′s rank correlation coefficient test. Results: IgM positivity confirmed acute infection in all 74 patients and of these 67 were vaccinated cases; however, very few of them (10/67 were positive for mumps IgG. We found that IFN-g, IL-2, and IL-10 showed a statistically significant increase in both pediatric and adult patients with acute mumps infection when compared to healthy controls and values were comparable to the positive control. Conclusion: The Th1 cells play important roles during the acute phase of mumps parotitis.

  2. Heavy metal mediated innate immune responses of the Indian green frog, Euphlyctis hexadactylus (Anura: Ranidae): Cellular profiles and associated Th1 skewed cytokine response

    Energy Technology Data Exchange (ETDEWEB)

    Jayawardena, Uthpala A.; Ratnasooriya, Wanigasekara D.; Wickramasinghe, Deepthi D.; Udagama, Preethi V., E-mail: dappvr@yahoo.com

    2016-10-01

    Immune cell and cytokine profiles in relation to metal exposure though much studied in mammals has not been adequately investigated in amphibians, due mainly to lack of suitable reagents for cytokine profiling in non-model species. However, interspecies cross reactivity of cytokines permitted us to assay levels of IFNγ, TNFα, IL6 and IL10in a common anuran, the Indian green frog (Euphlyctis hexadactylus), exposed to heavy metals (Cd, Cr, Cu, Zn and Pb, at ~ 5 ppm each) under field and laboratory settings in Sri Lanka. Enumeration of immune cells in blood and melanomacrophages in the liver, assay of serum and hepatic cytokines, and Th1/Th2 cytokine polarisation were investigated. Immune cell counts indicated overall immunosuppression with decreasing total WBC and splenocyte counts while neutrophil/lymphocyte ratio increased with metal exposure, indicating metal mediated stress. Serum IL6 levels of metal exposed frogs reported the highest (~ 9360 pg/mL) of all cytokines tested. Significantly elevated IFNγ production (P < 0.05) was evident in heavy metal exposed frogs. Th1/Th2 cytokine ratio in both serum and liver tissue homogenates was Th1 skewed due to significantly higher production of pro-inflammatory cytokines, IFNγ in serum and TNFα in the liver (P < 0.01).Metal mediated aggregations of melanomacrophages in the liver were positively and significantly (P < 0.05) correlated with the hepatic expression of TNFα, IL6 and IL10 activity. Overall, Th1 skewed response may well be due to oxidative stress mediated nuclear factor κ-light chain enhancer of activated B cells (NFκB) which enhances the transcription of pro-inflammatory cytokines. Xenobiotic stress has recently imposed an unprecedented level of threat to wildlife, particularly to sensitive species such as amphibians. Therefore, understanding the interactions between physiological stress and related immune responses is fundamental to conserve these environmental sentinels in the face of emerging eco

  3. CYTOKINE PROFILE OF TH1- AND TH2-DEPENDENT VARIANTS OF CHRONIC GVHD

    Directory of Open Access Journals (Sweden)

    O. T. Kudaeva

    2012-01-01

    Full Text Available Abstract. Induction of chronic GVHD in the DBA/2→(C57Bl/6xDBA/2 F1 semi-allogeneic murine model results into development of Th1- and Th2-dependent immunopathological conditions that are characterized by different cytokine profiles. Chronic GVHD is accompanied by a sharp increase in IgE levels, thus presuming considerable IL-4 production. In recipients with Th2-dependent GvHD variant, elevated contents of serum IL-6, IL-7 and TNFα were also observed, which, along with other effects, may support polyclonal activation of B cells, thus leading to development of autoimmune pathology.

  4. Pivotal Advance: Th-1 cytokines inhibit, and Th-2 cytokines promote fibrocyte differentiation

    OpenAIRE

    Shao, Diane D.; Suresh, Rahul; Vakil, Varsha; Gomer, Richard H.; Pilling, Darrell

    2008-01-01

    CD14+ peripheral blood monocytes can differentiate into fibroblast-like cells called fibrocytes, which are associated with and are at least partially responsible for wound healing and fibrosis in multiple organ systems. Signals regulating fibrocyte differentiation are poorly understood. In this study, we find that when added to human PBMCs cultured in serum-free medium, the profibrotic cytokines IL-4 and IL-13 promote fibrocyte differentiation without inducing fibrocyte or fibrocyte precursor...

  5. Pivotal Advance: Th-1 cytokines inhibit, and Th-2 cytokines promote fibrocyte differentiation.

    Science.gov (United States)

    Shao, Diane D; Suresh, Rahul; Vakil, Varsha; Gomer, Richard H; Pilling, Darrell

    2008-06-01

    CD14+ peripheral blood monocytes can differentiate into fibroblast-like cells called fibrocytes, which are associated with and are at least partially responsible for wound healing and fibrosis in multiple organ systems. Signals regulating fibrocyte differentiation are poorly understood. In this study, we find that when added to human PBMCs cultured in serum-free medium, the profibrotic cytokines IL-4 and IL-13 promote fibrocyte differentiation without inducing fibrocyte or fibrocyte precursor proliferation. We also find that the potent, antifibrotic cytokines IFN-gamma and IL-12 inhibit fibrocyte differentiation. In our culture system, IL-1beta, IL-3, IL-6, IL-7, IL-16, GM-CSF, M-CSF, fetal liver tyrosine kinase 3, insulin growth factor 1, vascular endothelial growth factor, and TNF-alpha had no significant effect on fibrocyte differentiation. IL-4, IL-13, and IFN-gamma act directly on monocytes to regulate fibrocyte differentiation, and IL-12 acts indirectly, possibly through CD16-positive NK cells. We previously identified the plasma protein serum amyloid P (SAP) as a potent inhibitor of fibrocyte differentiation. When added together, the fibrocyte-inhibitory activity of SAP dominates the profibrocyte activities of IL-4 and IL-13. The profibrocyte activities of IL-4 and IL-13 and the fibrocyte-inhibitory activities of IFN-gamma and IL-12 counteract each other in a concentration-dependent manner. These results indicate that the complex mix of cytokines and plasma proteins present in inflammatory lesions, wounds, and fibrosis will influence fibrocyte differentiation.

  6. Detection of intracytoplasmic Th1/Th2 cytokine profiles in patients with sepsis and severe sepsis

    Directory of Open Access Journals (Sweden)

    Ahmadinejad Z

    2007-06-01

    Full Text Available Background: Sepsis is the leading cause of death in critically ill patients throughout the world. The incidence is increasing despite the major advances in the development of antimicrobial agents and other supportive treatments. Based on multiple studies, it has been shown that patient outcome depends on Th1 and Th2 cytokine response. Moreover, whenever the Th2 response is predominant, the sepsis is more severe. The aim of this study was to evaluate the correlation between cytokine levels and the severity of sepsis in patients. Methods: A cross-sectional study on the cellular levels of several pro-inflammatory cytokines was carried out in patients with sepsis and severe sepsis. The study included 37 patients (24 men and 13 women, 26 of them had sepsis and 11 had the severe form of sepsis Thirty-seven healthy volunteers served as controls. The average age of the patients was 57 years (±23.3 years, with a range of 21 to 92 years. From the whole blood of the subjects, we separated the monocytes and leukocytes, which were then cultured. Using an ELISA method, we measured levels of IFN- and IL-12 (associated with Th1, and IL-4 and IL-10 (associated with Th2 in the cultured cells with and without cell stimulation. Results: No correlation was found for IFN- production in the cells of patients with sepsis and severe sepsis, regardless of whether the patients had died or survived. However, IL-12 levels were significantly decreased in severe sepsis compared with those of sepsis patients (P=0.048. Furthermore, the cells of expired patients also had significantly decreased IL-12 levels compared with those of surviving patients (P=0.028. We also found that the levels of IFN-, IL-4, and IL-10 were decreased in patients compared with those of controls, which correlated to their production. However, there was no correlation for IL-12 production between the cells of the patients compared with those of the controls. There was also no correlation for

  7. Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma.

    Science.gov (United States)

    Chen, Yingtai; Zheng, Tongzhang; Lan, Qing; Foss, Francine; Kim, Christopher; Chen, Xuezhong; Dai, Min; Li, Yumin; Holford, Theodore; Leaderer, Brian; Boyle, Peter; Chanock, Stephen J; Rothman, Nathaniel; Zhang, Yawei

    2011-01-13

    We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m(2), women with BMI more than or equal to 25 kg/m(2) had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 P(forinteraction) = .034) and IL7R (rs1494555 P(forinteraction) = .016) for NHL overall; IL7R (rs1494555 P(forinteraction) = .016) and TNF (1799724 P(forinteraction) = .031) for B-cell lymphoma; and IL5 (rs2069812 P(forinteraction) = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 P(forinteraction) = .006), IL13 (rs20541 P(forinteraction) = .019), and IL7R (rs1494555 P(forinteraction) = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 P(forinteraction) = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 P(forinteraction) = .013) and TNF (1799724 P(forinteraction) = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.

  8. SHARPIN is essential for cytokine production, NF-κB signaling, and induction of Th1 differentiation by dendritic cells.

    Science.gov (United States)

    Wang, Zhe; Sokolovska, Anna; Seymour, Rosemarie; Sundberg, John P; Hogenesch, Harm

    2012-01-01

    Spontaneous mutations of the Sharpin (SHANK-associated RH domain-interacting protein, other aliases: Rbckl1, Sipl1) gene in mice result in systemic inflammation that is characterized by chronic proliferative dermatitis and dysregulated secretion of T helper1 (Th1) and Th2 cytokines. The cellular and molecular mechanisms underlying this inflammatory phenotype remain elusive. Dendritic cells may contribute to the initiation and progression of the phenotype of SHARPIN-deficient mice because of their pivotal role in innate and adaptive immunity. Here we show by flow cytometry that SHARPIN- deficiency did not alter the distribution of different DC subtypes in the spleen. In response to TOLL-like receptor (TLR) agonists LPS and poly I:C, cultured bone marrow-derived dendritic cells (BMDC) from WT and mutant mice exhibited similar increases in expression of co-stimulatory molecules CD40, CD80, and CD86. However, stimulated SHARPIN-deficient BMDC had reduced transcription and secretion of pro-inflammatory mediators IL6, IL12P70, GMCSF, and nitric oxide. Mutant BMDC had defective activation of NF-κB signaling, whereas the MAPK1/3 (ERK1/2) and MAPK11/12/13/14 (p38 MAP kinase isoforms) and TBK1 signaling pathways were intact. A mixed lymphocyte reaction showed that mutant BMDC only induced a weak Th1 immune response but stimulated increased Th2 cytokine production from allogeneic naïve CD4(+) T cells. In conclusion, loss of Sharpin in mice significantly affects the immune function of DC and this may partially account for the systemic inflammation and Th2-biased immune response.

  9. SHARPIN is essential for cytokine production, NF-κB signaling, and induction of Th1 differentiation by dendritic cells.

    Directory of Open Access Journals (Sweden)

    Zhe Wang

    Full Text Available Spontaneous mutations of the Sharpin (SHANK-associated RH domain-interacting protein, other aliases: Rbckl1, Sipl1 gene in mice result in systemic inflammation that is characterized by chronic proliferative dermatitis and dysregulated secretion of T helper1 (Th1 and Th2 cytokines. The cellular and molecular mechanisms underlying this inflammatory phenotype remain elusive. Dendritic cells may contribute to the initiation and progression of the phenotype of SHARPIN-deficient mice because of their pivotal role in innate and adaptive immunity. Here we show by flow cytometry that SHARPIN- deficiency did not alter the distribution of different DC subtypes in the spleen. In response to TOLL-like receptor (TLR agonists LPS and poly I:C, cultured bone marrow-derived dendritic cells (BMDC from WT and mutant mice exhibited similar increases in expression of co-stimulatory molecules CD40, CD80, and CD86. However, stimulated SHARPIN-deficient BMDC had reduced transcription and secretion of pro-inflammatory mediators IL6, IL12P70, GMCSF, and nitric oxide. Mutant BMDC had defective activation of NF-κB signaling, whereas the MAPK1/3 (ERK1/2 and MAPK11/12/13/14 (p38 MAP kinase isoforms and TBK1 signaling pathways were intact. A mixed lymphocyte reaction showed that mutant BMDC only induced a weak Th1 immune response but stimulated increased Th2 cytokine production from allogeneic naïve CD4(+ T cells. In conclusion, loss of Sharpin in mice significantly affects the immune function of DC and this may partially account for the systemic inflammation and Th2-biased immune response.

  10. Th1/Th2 cytokines' expression and production by propolis-treated mice.

    Science.gov (United States)

    Orsatti, Cláudio Lera; Missima, Fabiane; Pagliarone, Ana Carolina; Sforcin, José Maurício

    2010-06-16

    Propolis is a natural product extensively used in food and beverages to improve health and to prevent diseases, showing immunomodulatory properties. The goal of this work was to evaluate the effect of propolis administration over a short-term to mice on Th1 (IL-2 and IFN-gamma) and Th2 (IL-4 and IL-10) cytokines' expression and production. Propolis was administered for 3 days to mice by gavage, spleens were removed and RNA was extracted to assess cytokines' expression by real-time PCR. Supernatants of spleen cell cultures were used for cytokines determination by ELISA. Propolis administration to mice did not affect IL-2, IL-4 and IL-10 expression and production, while IFN-gamma production was inhibited in the splenocyte cultures stimulated or not by Con A. Since IFN-gamma is a pro-inflammatory cytokine, our data suggest that propolis administration over a short-term to mice may be associated with anti-inflammatory effects in vivo, and further assays could check propolis efficiency in inflammatory diseases. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Change of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    Shi-Hua Zhou

    2016-01-01

    Objective:To analyze and investigate the change state of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion. Methods: A total of 92 patients with recurrent spontaneous abortion in our hospital from June 2013 to July 2015 were selected as the observation group and 92 women with health delivery history at the same time were selected as the control group,then the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of two groups were detected and compared and the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of patients with different gestational age at abortion and abortion times were compared too. Results:The peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of observation group and control group all had obvious differences,and those blood indexes levels' differences of patients with different gestational age at abortion and abortion times were obvious too, all P<0.05 and the differences were significant. Conclusions: The T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion show abnormal state and the differences of detection results of patients with different gestational age at abortion and abortion times are relatively obvious,so those indexes should be monitored and improved intentinonally.

  12. Preferential Th1 cytokine profile of phosphoantigen-stimulated human Vγ9Vδ2 T cells.

    LENUS (Irish Health Repository)

    Dunne, Margaret R

    2010-01-01

    Human Vγ9Vδ2 T cells recognise pyrophosphate-based antigens (phosphoantigens) and have multiple functions in innate and adaptive immunity, including a unique ability to activate other cells of the immune system. We used flow cytometry and ELISA to define the early cytokine profiles of Vγ9Vδ2 T cells stimulated in vitro with isopentenyl pyrophosphate (IPP) and (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate (HMB-PP) in the absence and presence of IL-2 and IL-15. We show that fresh Vγ9Vδ2 T cells produce interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) within 4 hours of stimulation with phosphoantigen, but neither IL-10, IL-13, nor IL-17 was detectable up to 72 hours under these conditions. Cytokine production was not influenced by expression or lack, thereof, of CD4 or CD8. Addition of IL-2 or IL-15 caused expansion of IFN-γ-producing Vγ9Vδ2 T cells, but did not enhance IFN-γ secretion after 24-72 hours. Thus, phosphoantigen-stimulated Vγ9Vδ2 T cells have potential as Th1-biasing adjuvants for immunotherapy.

  13. Ship-borne journey induces Th1 cytokines level in antarctic summer expeditioners.

    Science.gov (United States)

    Mishra, Kamla Prasad; Yadav, Anand Prakash; Shweta; Chanda, Sudipta; Ganju, Lilly; Majumdar, Dhurjati; Ilavazhagan, Govindasamy

    2010-01-01

    It has become apparent that extreme environmental conditions of Antarctic continent alters many immune responses. The present study was conducted on 28th Indian Antarctic expeditioners. The investigations were carried out to explore the effect of multiple stresses like isolation, cold and UV exposure on human immunity. Thirty blood samples were collected between 6 and 7 AM, after an overnight fast at different stages of the expedition - viz. the pre-exposure sample was collected at Delhi on 25(th) October 2008. The expedition started its ship journey from Capetown, on 6(th) January, 2009 and on-board blood was collected on 31(st) January 2009. After 1 month stay at Maitri, blood was collected on 3(rd) March 2009. Different parameters studied included levels of cytokines, chemokines and cortisol. The ship-borne journey induced a dramatic increase in TNF-α, IFN-γ, and B cell activating factor (BAFF) levels and moderate decreases in TGF-β and cortisol levels. However, after being off board for 1 month at Maitri station, levels of above cytokines, cortisol and BAFF were decreased but MIP-1α was significantly increased. These data for the first time suggest that ship-borne journey to the Antarctic continent results in tremendous stress to the body, which eventually resulted in increased TH1-biased immunity.

  14. Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71-associated meningoencephalitis.

    Science.gov (United States)

    Li, Huajun; Li, Shuxian; Zheng, Jianfeng; Cai, Chunyan; Ye, Bin; Yang, Jun; Chen, Zhimin

    2015-03-01

    Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ, in cerebrospinal fluid (CSF) from patients with EV71-related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL-6 and IFN-γ concentrations were significantly higher in patients with EV71-related ME than in those with FC. Additionally, both CSF IL-6 and IFN-γ concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL-6 and IFN-γ concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set for IL-6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71-related ME from FC. In conclusion, IL-6 and IFN-γ may be associated with EV71-induced neuropathology. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  15. Chronic pain: cytokines, lymphocytes and chemokines.

    Science.gov (United States)

    de Miguel, Marcia; Kraychete, Durval Campos; Meyer Nascimento, Roberto Jose

    2014-01-01

    Chronic pain is a debilitating condition and, in most cases, difficult to treat. A prominent example of this is neuropathic pain. Understanding pathophysiological mechanisms of pain and, therefore, making this knowledge into an effective treatment is still a challenge to experts. Pain can now be considered as a neuro-immune disorder, since recent data indicate critical involvement of innate and adaptive immune responses following injury, and this interaction plays an important role in the onset and perpetuation of chronic pain. The aim of this article is to review the relationship between immune system and chronic pain, especially about neuropathic pain, and focusing on cytokines, chemokines and lymphocytes.

  16. TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab

    Directory of Open Access Journals (Sweden)

    Oreja-Guevara Celia

    2012-09-01

    Full Text Available Abstract Background The balance between T helper cells Th2- and Th1-related cytokines plays a key role in multiple sclerosis (MS. A shift from a Th1 towards a Th2 cytokine profile could have a beneficial effect on the clinical course of the disease. The objective of this study was to assess Th2/Th1 cytokine profile in relapsing-remitting MS (RRMS patients receiving an immunosuppressive treatment with natalizumab (NAT, or an immunomodulatory treatment with glatiramer acetate (GA after one year of treatment. Methods This was an observational cross-sectional study. All consecutive patients diagnosed with RRMS who had received GA or NAT for 12 months were included in the study. We determined serum levels of Th1 and Th2 cytokines (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, monocyte chemotactic protein [MCP]-1, tumor-necrosis factor [TNF]-α, interferon [IFN]-γ and granulocyte macrophage colony stimulating factor [GM-CSF] by flow cytometry. Th2/Th1 bias was defined based on the ratio of IL-4, IL-5, IL-6 or IL-10 Th2 cytokines and proinflammatory INF-γ or TNF-α Th1 cytokines. Results Eleven patients under treatment with NAT and 12 patients treated with GA were evaluated. RRMS patients treated with NAT showed significantly higher levels of IL-6 (p  Conclusion In conclusion, our findings suggest that GA promotes a superior Th2-biased anti-inflammatory response as compared with NAT in the systemic circulation of RRMS patients. Future studies with larger cohorts will determine whether this immune Th2 shift in GA patients is associated with a beneficial effect on disease outcome.

  17. Changes and significances of Th1/Th2, related cytokines and T cell subgroup in aplastic anemia patients

    Institute of Scientific and Technical Information of China (English)

    Hong-Xia Zhang; Guang-Sheng Wu; Wei-Ling Guo

    2016-01-01

    Objective:To investigate the changes and significances of Th1/Th2, related cytokines and T cell subgroup in aplastic anemia(AA) patients.Methods:A total of 87 cases AA patients were chosen. They were set as observation group, and they were divided into acute group (n=21) and chronic group (n=66) according to the condition, chose another 30 cases healthy volunteers as control group, detected the Th1 cytokine interferon-γ (IFN-γ) and Th2 cytokines interleukin-4 (IL-4) with nzyme-linked immunosorbent method, detected the Th1/Th2 cells and T cells subgroup with flow cytometry instrument between groups.Results:The Th1 cells and Th1/Th2 cells in observation group were significantly higher than control group. Th1 cells and Th1/Th2 cells in acute group were significantly higher than chronic group; The IFN-γ, IL-4 and IFN-γ/IL-4 in observation group were significantly higher than that of control group, and the IFN-γ, IL-4 and IFN-γ/IL-4 in acute group were significantly higher than chronic group; The blood CD4+, CD4+/CD8+ in observation group were significantly lower than the control group, CD8+ was significantly higher than the control group, and the blood CD4+, CD4+/CD8+ in acute group were significantly lower than the chronic group, CD8+ was significantly higher than the chronic group, all the difference was statistically significant.Conclusion:T cell subgroup imbalances and Th1 migration plays the important role in the onset of AA, and may relate to a certain degree of disease state.

  18. Local Th1/Th2 Cytokine Expression in Experimental Murine Vaginal Candidiasis

    Institute of Scientific and Technical Information of China (English)

    Weixiang OUYANG; Shanjuan CHEN; Zhixiang LIU; Yan WU; Jiawen LI

    2008-01-01

    In order to investigate the expression of Th1 and Th2 cytokines in the vaginal candidiasis caused by Candida, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animals were pretreated with estradiol. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-2, IL-4, IL-10 and TGF-β1 in the vagina in the mice of different groups at different time points after the beginning of the experiment. The average expression level of IL-2 mRNA in group D (estrogen-treated mice) was significantly higher than that in groups H (estrogen-untreated mice) and I (control group) on the day 2. The average expression level of IL-4 mRNA in group D was significantly higher than that in groups I and H on the day 5. The average expression level of IL-10 mRNA in group D was significantly higher than that in groups H and I from day 7 to 11. The average expression level of TGF-β1 mRNA in group D was significantly higher than that in groups H and I at all time points. It was concludes that the high-level expression of IL-2 mRNA during early infection was associated with clearance of mucosal C. albicans, and the high-level expression of IL-10 mRNA during late stage of the infection was related to susceptibility to infection. TGF-β1 may play a predominant role when the virtual absence of changes in other Th-type cytokines during infection.

  19. Immunotoxicity of Hydrocortisone on Th1/Th2-Related Cytokine Production Is Associated with Yang-Deficient State in Traditional Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    Chengfang Yao; Li Wang; Jian Zhang; Xianbin Zhou; Cai Zhang

    2007-01-01

    Steroid hormone serving as an immunosuppressor often induces immunotoxicity when administered in highest dosage or accumulated in long-term usage. The stage of high concentration of steroid hormone leading to a wide range of symptoms is associated to the yang-deficient state, which is the part of yin-yang imbalance involved in processes of many diseases in traditional Chinese medicine. Here we intend to investigate the profile of Th1/Th2-related cytokine transcriptions under yang-deficient conditions in a yang-deficient animal model by intramuscular injection of hydrocortisone (a kind of steroid hormone). The yang-deficient symptoms were estimated by detecting activity, appetite, body weight and so on. T cell proliferation and cytokine transcriptions were analyzed. The results showed that yang-deficient mice were established successfully since typical yang-deficient symptoms were observed in this model with decreased activities, appetite, body weight and temperature. More interestingly, the transcriptions of IFN-γ, IL-2, IL-4 and IL-10 in this model were markedly suppressed and the proliferation of lymphocytes significantly decreased as well. The results suggested that yang-deficient symptoms were related to the steroid-induced reduction of cytokine transcription and impairment of lymphocyte proliferation. Therefore, novel strategies through regulating cytokine production might be considered as potent approach to patients with yang-deficiency symptoms.

  20. Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris

    Science.gov (United States)

    Timoteo, Rodolfo Pessato; Silva, Djalma Alexandre Alves; Catarino, Jonatas Da Silva; Rodrigues Junior, Virmondes

    2017-01-01

    Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum. PV patients had higher levels of inflammatory Th1/Th17 cytokines (IFN-γ, IL-17, and IL-23), as well as higher levels of CXCL8 and reduced levels of Th1/Th2-related chemokines (IP-10 and CCL11). However, no differences in the levels of IL-2, IL-6, TNF-α, IL-1β, IL-4, IL-9, IL-12, TGF-β, IL-33, MCP-1, RANTES, and MIP-1α were found between PV patients and their control counterparts. Furthermore, PV patients with skin lesions had higher serum levels of IL-6 and CXCL8 when compared to PV patients without lesions. Taken together, our findings describe the role of cytokines and chemokines associated with Th1/Th17 immune response in PV patients. Finally, these data are important for better understanding of the immune aspects that control disease outcome, and they may also provide important information about why patients develop autoantibodies against desmogleins. PMID:28321152

  1. Influence of Radix scutellariae on Th1/Th2 cytokine balance in RU486-induced abortion in mice

    Institute of Scientific and Technical Information of China (English)

    ZHONG Xiuhui; SHI Wanyu; MA Aituan; WANG Xiaodan; ZHANG Jianlou; LI Xuezhong

    2007-01-01

    The aim of this study is to investigate the significance of Th1/Th2 cytokine balance in the uterus in the early embryo loss(or resorption),and to elucidate immunological modulation at the maternal-fetal interface with Chinese herbal medicine Radix scutellariae(Huang Qin)and its constituents(Baicalin and Baicalein).Mifepristone(RU486)was given via subcutaneous injection in the scapular area to induce abortion in mice at day 7 of gestation.The levels of uterine Thl cytokines(IFN-β,IL-2)and Th2 cytokines(IL-4,IL-10)were analyzed by enzyme-linked immunosorbent assay(ELISA),respectively.The mean values of Thl cytokines in the uterus of RU486-treated abortion mice were significantly higher(P<0.05)than that of the control mice,but no significant difference was observed regarding to the contents of Th2 cytokines of different groups(P>0.05).However,when the Radix scutellariae and its constituents were used to prevent RU486-induced abortion,the levels of IFN-γ and IL-2 decreased while that of IL-4 and IL-10 increased.The embryo loss induced by RU486 was closely related to the Th1/Th2 immune balance at the maternal-fetal interface.Radix scutellariae and its constituents have an anti-abortive effect through restoring the Th1/Th2 balance at the maternal-fetal interface.

  2. T cell clones from Schistosoma haematobium infected and exposed individuals lacking distinct cytokine profiles for Th1/Th2 polarisation

    Directory of Open Access Journals (Sweden)

    Mduluza T

    2001-01-01

    Full Text Available T cell clones were derived from peripheral blood mononuclear cells of Schistosoma haematobium infected and uninfected individuals living in an endemic area. The clones were stimulated with S. haematobium worm and egg antigens and purified protein derivative. Attempts were made to classify the T cell clones according to production of the cytokines IL-4, IL-5 and IFN-gamma. All the T cell clones derived were observed to produce cytokines used as markers for the classification of Th1/Th2 subsets. However, the 'signature' cytokines marking each subset were produced at different levels. The classification depended on the dominating cytokine type, which was having either Th0/1 or Th0/2 subsets. The results indicated that no distinct cytokine profiles for polarisation of Th1/Th2 subsets were detected in these S. haematobium infected humans. The balance in the profiles of cytokines marking each subset were related to infection and re-infection status after treatment with praziquantel. In the present study, as judged by the changes in infection status with time, the T cell responses appeared to be less stable and more dynamic, suggesting that small quantitative changes in the balance of the cytokines response could result in either susceptibility or resistant to S. haematobium infection.

  3. Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium tuberculosis Infection in HIV-Infected Individuals.

    Science.gov (United States)

    Ly, Judy; Lagman, Minette; Saing, Tommy; Singh, Manpreet Kaur; Tudela, Enrique Vera; Morris, Devin; Anderson, Jessica; Daliva, John; Ochoa, Cesar; Patel, Nishita; Pearce, Daniel; Venketaraman, Vishwanath

    2015-11-01

    Cytokines are signaling biomolecules that serve as key regulators of our immune system. CD4(+) T-cells can be grouped into 2 major categories based on their cytokine profile: T-helper 1 (TH1) subset and T-helper 2 (TH2) subset. Protective immunity against HIV infection requires TH1-directed CD4 T-cell responses, mediated by cytokines, such as interleukin-1β (IL-1β), IL-12, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). Cytokines released by the TH1 subset of CD4 T-cells are considered important for mediating effective immune responses against intracellular pathogens such as Mycobacterium tuberculosis (M. tb). Oxidative stress and redox imbalance that occur during HIV infection often lead to inappropriate immune responses. Glutathione (GSH) is an antioxidant present in nearly all cells and is recognized for its function in maintaining redox homeostasis. Our laboratory previously reported that individuals with HIV infection have lower levels of GSH. In this study, we report a link between lower levels of GSH and dysregulation of TH1- and TH2-associated cytokines in the plasma samples of HIV-positive subjects. Furthermore, we demonstrate that supplementing individuals with HIV infection for 13 weeks with liposomal GSH (lGSH) resulted in a significant increase in the levels of TH1 cytokines, IL-1β, IL-12, IFN-γ, and TNF-α. lGSH supplementation in individuals with HIV infection also resulted in a substantial decrease in the levels of free radicals and immunosuppressive cytokines, IL-10 and TGF-β, relative to those in a placebo-controlled cohort. Finally, we determined the effects of lGSH supplementation in improving the functions of immune cells to control M. tb infection by conducting in vitro assays using peripheral blood mononuclear cells collected from HIV-positive individuals at post-GSH supplementation. Our studies establish a correlation between low levels of GSH and increased susceptibility to M. tb infection through TH2-directed response

  4. Influence of DC-CIK in advanced colorectal cancer patients on T lymphocyte subsets and cytokines

    Institute of Scientific and Technical Information of China (English)

    Rong Wang; Min Yi; Shi-Rong Yang; Li-Xia Chai; Mao Hua

    2016-01-01

    Objective:To explore the effects of dendritic cells (DC)-cytokine induced killer cells (CIK) treatment on T lymphocyte subsets and cytokines in patients with advanced colorectal cancer. Methods:A total of 84 cases patients with advanced colorectal cancer were divided into two groups according to random number table method, each 42 cases, both two groups were given FOLFOX scheme chemotherapy, on the basis, the observation group were given supplementary DC-CIK treatment, compared the T lymphocy te subgroup: CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines, interleukin-2 (IL-2) and interferon gamma-γ (FN-γ), Th2 cytokines:interleukin 6 (IL-6), interleukin 4 (IL-4) of the two groups before and after treatment. Results:Compared with before treatment, the CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γin observation group were significantly higher than after treatment , the CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γin control group were significantly lower than after treatment, and the differences were all statistically significant;The CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γin observation group after treatment were significantly higher than those in control group after treatment with statistical difference;CD8+, Th2 cytokines IL-4, IL-6 in two groups had no statistical significance before and after treatment. Conclusion:Chemotherapy can cause the immune function restrained in patients with advanced colorectal cancer, and DC-CIK supplementary therapy can significantly improve the immune function, enhance the anti tumor immune responses.

  5. Serum levels of Th1/Th2 cytokines in aged patients and their correlation with eczema development and clinical manifestation

    Institute of Scientific and Technical Information of China (English)

    Wei-Gang Wang; Feng-Lin Hou; Xiu-Ming Zhang; Shi-Wu Ma; Jin-Jun Chen

    2016-01-01

    Objective:To investigate variations of Th1/Th2 cytokine levels, as well as their correlation with eczema development and clinical manifestation in aged patients.Methods: A total of 92 patients (above 60 years old) with eczema diagnosed by the outpatient department of dermatology and venerology of our hospital were included as the eczema group, while 60 aged patients without eczema as the healthy group. Patients' serum levels of Th1/Th2 cytokines were examined for inter-group comparison and stratified analysis as per clinical manifestation. Results:Serum levels of interleukin (IL)-2, IL-4, IL-10, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were all significantly higher in patients of the eczema group than the healthy group. Acute stage levels of IL-2, IL-4, IL-10 and IFN-γ were significantly higher in patients of the eczema group than the healthy group. There was no significant difference in the levels of IL-12 and TNF-α between patients of the acute stage and those of the chronic stage. And no significant difference existed in the levels of IL-2, IL-4, IL-10, IL-12, TNF-α and IFN-γ between generalized and localized eczema patients.Conclusion:Compared with the healthy population, Th1/Th2 cytokine levels are significantly different in eczema patients, especially those in the acute stage.

  6. Advances of materia medica in adjusting Th1/Th2 cytokines balance%中药对Th1/Th2细胞因子平衡调节作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    袁颖; 金素安; 何世民

    2011-01-01

    This paper reviews the regulating effects of materia medica on Th1/Th2 cytokine balance in autoimmune diseases, cancer, allergic diseases and different Chinese medicine syndromes.%概述中药对Th1/Th2平衡的调节作用,主要包括中药对自身免疫疾病Th1/Th2平衡的影响、对肿瘤Th1/Th2平衡的影响、对变态反应性疾病Th1/Th2平衡的影响以及对不同中医证型Th1/Th2平衡的影响等.

  7. TH1 and TH2 cytokine data in insulin secretagogues users newly diagnosed with breast cancer

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    Zachary A.P. Wintrob

    2017-04-01

    Full Text Available Stimulation of insulin production by insulin secretagogue use may impact T helper cells’ cytokine production. This dataset presents the relationship between baseline insulin secretagogues use in women diagnosed with breast cancer and type 2 diabetes mellitus, the T-helper 1 and 2 produced cytokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between T-helper cytokines stratified by of insulin secretagogues use and controls is also provided.

  8. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins

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    Nedelkoska Liljana

    2007-12-01

    Full Text Available Abstract Background In multiple sclerosis, inflammatory cells are found in both active and chronic lesions, and it is increasingly clear that cytokines are involved directly and indirectly in both formation and inhibition of lesions. We propose that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages each induce unique molecular changes in glial cells. Methods To examine changes in gene expression that might occur in glial cells exposed to the secreted products of immune cells, we have used gene array analysis to assess the early effects of different cytokine mixtures on mixed CNS glia in culture. We compared the effects of cytokines typical of Th1 and Th2 lymphocytes and monocyte/macrophages (M/M on CNS glia after 6 hours of treatment. Results In this paper we focus on changes with potential relevance for neuroprotection and axon/glial interactions. Each mixture of cytokines induced a unique pattern of changes in genes for neurotrophins, growth and maturation factors and related receptors; most notably an alternatively spliced form of trkC was markedly downregulated by Th1 and M/M cytokines, while Th2 cytokines upregulated BDNF. Genes for molecules of potential importance in axon/glial interactions, including cell adhesion molecules, connexins, and some molecules traditionally associated with neurons showed significant changes, while no genes for myelin-associated genes were regulated at this early time point. Unexpectedly, changes occurred in several genes for proteins initially associated with retina, cancer or bone development, and not previously reported in glial cells. Conclusion Each of the three cytokine mixtures induced specific changes in gene expression that could be altered by pharmacologic strategies to promote protection of the central nervous system.

  9. Th17 and Th1 Lymphocytes Are Correlated with Chronic Periodontitis.

    Science.gov (United States)

    Chen, Xiao-Tao; Chen, Li-Li; Tan, Jing-Yi; Shi, Dan-Hui; Ke, Ting; Lei, Li-Hong

    2016-01-01

    T cells are involved in the homeostasis of periodontal tissues and mediate bone loss in periodontitis, but the involvement of T-helper cells in chronic periodontitis (CP) in a Chinese population is still unclear. This study aimed to assess the distribution of peripheral and local T helper (Th17) and Th1 in CP. Sixty-eight patients with CP and 43 healthy controls were recruited from April 2012 to July 2014 at the Department of Stomatology, People's Hospital of Xinjiang Uygur Autonomous Region (China). The proportions of Th17 (CD3(+)CD4(+)IL-17(+)) and Th1 (CD3(+)CD4(+)IFN-γ(+)) T-cells in peripheral blood samples were assessed by flow cytometry. Immunohistochemistry was used to quantify interleukin-17 (IL-17) and interferon-gamma (IFN-γ) protein levels in gingival biopsy samples. mRNA levels of IL-17, IFN-γ RORγt, and T-bet in gingival biopsy samples were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proportions of circulating Th17 cells and Th1 cells were both more abundant in CP patients than in controls (Th17: 1.05% ± 0.87% vs. 0.62% ± 0.49%, P < 0.01; Th1: 13.93% ± 7.94% vs. 8.22% ± 4.50%, P < 0.001). Positive correlations were obtained between the proportion of circulating Th17 cells and probing depth (PD) (r = 0.320, P = 0.001) and between the proportion of circulating Th1 cells and PD (r = 0.372, P < 0.001). IL-17 and IFN-γ protein levels in gingival biopsy samples were markedly increased in CP compared to controls (both P < 0.05). Relative IFN-γ, IL-17A, and T-bet mRNA levels in CP biopsies were higher compared to controls (all P < 0.05). These results suggest that elevated peripheral and local Th17 and Th1 cells might be involved in the pathogenesis of CP.

  10. A novel role of IGFBP7 in mouse uterus: regulating uterine receptivity through Th1/Th2 lymphocyte balance and decidualization.

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    Zhen-Kun Liu

    Full Text Available Previously we have screened out Insulin-like Growth Factor Binding Protein 7 (IGFBP7 as a differentially expressed gene in post-implantation uterus versus pre-implantation uterus by suppressive subtractive hybridation. However its function in uterus was not clearly identified. In this research, the expression and function of IGFBP7 during post-implantation were studied. We found that IGFBP7 was mainly located in the glandular epithelium and the stroma, and was upregulated after embryo implantation. The vector pCR3.1-IGFBP7-t expressing partial IGFBP7 was constructed. Inhibition of IGFBP7 by specific DNA immunization induced significant reduction of implanted embryos and pregnancy rate. The number of implanted embryos (5.68 ± 0.46 was significantly reduced after immunization with pCR3.1-IGFBP7-t, as compared with that of the mice immunized with the control vector (12.29 ± 0.36 or saline (14.58 ± 0.40 (p<0.01. After specific inhibition of IGFBP7, the T helper type 1 (Th1 cytokine IFNγ, was significantly elevated (p<0.05 and the Th2 cytokines IL-4 and IL-10, were reduced in uteri (p<0.05. The increase of Tbet and the decrease of Gata3 were found in mice peripheral lymphocytes by flow cytometry. The expression of decidualization marker IGFBP1 and angiogenesis regulator VEGF were declined in uteri (p<0.05. The expression of apoptosis-associated proteins, caspase3 and Bcl-2, were also declined (p<0.05. These results showed that inhibition of IGFBP7 induced pregnancy failure by shifting uterine cytokines to Th1 type dominance and repressing uterine decidualization.

  11. Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia

    OpenAIRE

    Janikashvili, Nona; LaCasse, Collin J.; Larmonier, Claire; Trad, Malika; Herrell, Amanda; Bustamante, Sara; Bonnotte, Bernard; Har-Noy, Michael; Larmonier, Nicolas; Katsanis, Emmanuel

    2011-01-01

    Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4+ T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4+CD25+FoxP3+ regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generatio...

  12. [Lymphocyte subsets, dendritic cells and cytokine profiles in mice with melanoma treated with Uncaria tomentosa].

    Science.gov (United States)

    Lozada-Requena, Iván; Núñez, César; Alvárez, Yubell; Kahn, Laura; Aguilar, José

    2015-10-01

    To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the plant. All cell assays and cytokine measurements were performed by flow cytometry. UT-POA systemically increased CD4/CD8a relation while cell activation was inversely proportional; increased the proportion of DCm; induced a pro-inflammatory Th1 profile and reduced Th17 response. TNF-α and IL-17A positively and negatively correlated with CD4/CD8a relation. The increase of Th1 (TNF-α) may result in the increase of CD4 or M1 macrophage activation. Although UT-POA shows increased DCm, is not dose-dependent. Th17(IL-17A) decreased can support the function of CD8a lymphocytes. UT-POA shows better systemic immunomodulatory effects than intratumoral.

  13. Inactivated Parapoxvirus ovis induces a transient increase in the expression of proinflammatory, Th1-related, and autoregulatory cytokines in mice

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    Anziliero, D.; Weiblen, R. [Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil, Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Kreutz, L.C. [Programa de Pós-Graduação em Bioexperimentação, Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo, Passo Fundo, RS, Brasil, Programa de Pós-Graduação em Bioexperimentação, Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo, Passo Fundo, RS (Brazil); Spilki, F. [Laboratório de Microbiologia Molecular, Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS, Brasil, Laboratório de Microbiologia Molecular, Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS (Brazil); Flores, E.F. [Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil, Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

    2014-02-17

    The immunostimulatory properties of inactivated Parapoxvirus ovis (iPPVO) have long been investigated in different animal species and experimental settings. In this study, we investigated the effects of iPPVO on cytokine expression in mice after intraperitoneal inoculation. Spleen and sera collected from iPPVO-treated mice at intervals after inoculation were submitted to cytokine mRNA determination by real-time PCR (qPCR), serum protein concentration by ELISA, and interferon (IFN)-α/β activity by bioassay. The spleen of iPPVO-treated animals showed a significant increase in mRNA expression of all cytokines assayed, with different kinetics and magnitude. Proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), and IL-8 mRNA peaked at 24 hours postinoculation (hpi; 5.4-fold increase) and 48 hpi (3- and 10-fold increases), respectively. A 15-fold increase in IFN-γ and 6-fold IL-12 mRNA increase were detected at 48 and 24 hpi, respectively. Increased expression of autoregulatory cytokines (Th2), mainly IL-10 and IL-4, could be detected at later times (72 and 96 hpi) with peaks of 4.7- and 4.9-fold increases, respectively. IFN-I antiviral activity against encephalomyocarditis virus was demonstrated in sera of treated animals between 6 and 12 hpi, with a >90% reduction in the number of plaques. Measurement of serum proteins by ELISA revealed increased levels of IL-1, TNF-α, IL-12, IFN-γ, and IL-10, with kinetics similar to those observed by qPCR, especially for IL-12 and IFN-γ. These data demonstrate that iPPVO induced a transient and complex cytokine response, initially represented by Th1-related cytokines followed by autoregulatory and Th2 cytokines.

  14. Evaluation of Th1 and Th17 cells cytokines in cell culture stimulated in women with recurrent spontaneous abortion

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    Y Varghaiyan

    2013-10-01

    Full Text Available Introduction: Various immunological abnormalities have been reported in women with RSA of unknown aetiologies including autoimmune abnormalities and increased cellular immunity such as elevated natural killer (NK , Th1 and Th17 cell levels. Th17 and Th1 cells play a central role during inflammation. Th1 cells product cytokines IFN-γ, IL-2 and Th17 cells mainly cytokines IL-17A, F, IL-22. The aim of this study is evaluation of Th1 and Th17 activity in women with recurrent spontaneous abortion. Methods: In this case-control study, 30 women with history of two or more abortion who at least 3 months past after last abortion considered as case group and 30 normal fertile healthy women with at least one delivery as control group. We determined the levels of IL-17A, F and IFN-γ in cell culture supernatant of peripheral blood mononuclear cells (PBMC stimulated with the mitogen phytohemagglutinin (PHA by enzyme-linked immunosorbent assay (ELISA method and compared in the two groups. The results obtained using the one-sample kolmogorov-smirnov Test, Kruskal-wallis Test and Spearman were analyzed using SPSS 16 software. Results: The level of IFN- γ in case group was significantly higher than control group (186/53±30/41 versus 88/06±21/44 pg/ml, P < 0.005. Also the level of IL-17 A, F in case group was significantly higher than control group (84/74±21/26 versus 28/41±8 pg/ml, P < 0.01. IFN-γ concentration showed positive correlation with IL-17 A, F in case group (P=0.015, r= 0.455. Conclusion: In this study the increased levels of cytokines IFN- γ and IL-17 A, F in women with recurrent spontaneous abortion shows a propensity of pro inflammation via Th17 and Th1 immunity and may be these cells play a pivotal role in rejecting fetus antigens.

  15. Lymphocyte subsets, dendritic cells and cytokine profiles in mice with melanoma treated with Uncaria tomentosa

    OpenAIRE

    Lozada-Requena, Iván; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú. EMINDES SAC (empresa de investigación y desarrollo en cáncer). Lima, Perú.; Núñez, César; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú. EMINDES SAC (empresa de investigación y desarrollo en cáncer). Lima, Perú.; Alvárez, Yubell; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.; Kahn, Laura; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.; Aguilar, José; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.

    2015-01-01

    Objectives. To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Materials and methods: Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the pl...

  16. Retinol levels, iron status, malaria and intestinal parasites: TH1/TH2 cytokines relationship.

    Directory of Open Access Journals (Sweden)

    Viviana Taylor

    2009-11-01

    Full Text Available Introducción: La malaria, la anemia y la parasitosis intestinal coexisten y constituyen problemas de salud pública en Colombia. Datos disponibles en la literatura biomédica llevan a pensar que estos problemas no son aislados sino que están interrelacionados. Por otra parte, los suplementos de retinol han sido efectivos para reducir la mortalidad infantil, con disminución de complicaciones en niños palúdicos, posiblemente por efectos del retinol sobre la función inmune, desviando la respuesta de citocinas hacia un patrón TH2, que también protege de desarrollar anemia grave. Esta revisión tiene como objetivo describir parte de las relaciones vistas en la literatura biomédica mundial, entre retinol y malaria, retinol y anemia, retinol, malaria y parasitosis intestinal, anemia y malaria y mostrar la mediación de estas interrelaciones por el patrón de citocinas TH1/TH2 en sujetos con malaria. Metodología: Se consultaron las siguientes bases de literatura biomédica: Medline, Lilacs, Spingerlik, Md Consultant, Web of Science, Ovid, Scient Direct, Ebsco y Cochrane. También se buscó información para documentar la prevalencia de desnutrición, deficiencia subclínica de retinol, anemia y malaria en niños colombianos, lo mismo que sobre el papel antinfeccioso del retinol. Resultados: Existe asociación entre parasitosis intestinal y malaria; algunos estudios indican que los helmintos predisponen a contraer malaria en niños. De otro lado, los parásitos mencionados, también se han relacionado con anemia y bajas concentraciones plasmáticas de retinol, que a la vez se asocian con malaria. Sin embargo, no se encontró información que relacione simultáneamente todos estos tópicos y que muestre la respuesta de citocinas TH1/TH2 como la articulación de todos ellos. Conclusiones: Aclarar las múltiples interacciones entre malaria, anemia, parasitosis intestinal y deficiencia subclínica de retinol, teniendo como eje central la respuesta

  17. Local Expression of Vaginal Th1 and Th2 Cytokines in Murine Vaginal Candidiasis under Different Immunity Conditions

    Institute of Scientific and Technical Information of China (English)

    Shanjuan CHEN; Shaohua LI; Yan WU; Zhixiang LIU; Jiawen LI

    2008-01-01

    To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed murine models of vaginal cadidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls. The mRNA level of Th1(IL-2)/Th2 (IL-4, IL-10, TGF-β1) cytokines in murine vaginal tissues was determined by RT-PCR.The cykotine in local tissues was increased to different extent under normal immune condition. IL-2mRNA was increased during early stage of infection, while IL-10 was increased transiently during late stage of infection. TGF-β1 production was found to be increased persistently. At same time, the expression of IL-2 mRNA was suppressed in immno-suppressed group, and the level of IL-4, IL-10,and TGF-β1 were higher than the normal immunity group to different degree during infection. The high level of IL-2 mRNA during early stage of infection was associated with clearance of mucosal Candidia albicans (C. albicans), and its expression suppressed leading to decreased clearance of mucosal C. albican in immuno-suppression. The over-expression of IL-4 and IL-10 could significantly enhance the susceptibility to C. albicans infection in mice.

  18. The Comparison of TH1 and TH2 Cytokines Gene Expression in Allergic and Non-Allergic Patients With Nasal Polyps By PCR

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    Javadinia Sh

    2011-12-01

    Full Text Available Background: Too many studies are in the process of determining the probable role of immune system in the etiopathogenesis of nasal polyposis. This study was designed to identify the probable participation of Th1, Th2 lymphocytes in the induction and progression of nasal polyposis.Methods: Seventy-five patients, 42 male and 33 female, with nasal polyposis were examined for total serum IgE, specific serum IgE and reaction to skin test for differentiating allergic from non-allergic participants in Rasoul Akram Hospital during 2010. To determine the possible correlation of allergic reactions in the upper respiratory tract and nasal polyposis, cytokine gene expression was evaluated on the extracted RNA by RT-PCR. The data were analyzed by using c2, independent t-test, correlation and Receiver operating characteristic (ROC curve.Results: The mean age of participants was 38 years (18-81 years. IFN-γ and IL-4 gene expressions were more prevalent in allergic than non-allergic individuals (IFN-γ: 39.5% vs. 14.2%, P=0.3 and IL-4: 44.7% vs. 18.9%, P=0.02, respectively. IL-10 and IL-12 (P35 and P40 fractions genes were not significantly different between the two groups. IL-10 and IL-12 (P35, P40 genes did not differ significantly either.Conclusion: This research suggests that overproduction of cytokines and an imbalance of Th1 and Th2 cell production may play an important role in the pathophysiology of allergic or non-allergic nasal polyp formation. Thus, although nasal polyposis is a multifactorial disease with several different etiological factors, chronic persistent inflammation is undoubtedly a major factor irrespective of the etiology.

  19. Differential Interactions between Th1/Th2, Th1/Th3, and Th2/Th3 Cytokines in the Regulation of Thyroperoxidase and Dual Oxidase Expression, and of Thyroglobulin Secretion in Thyrocytes in Vitro

    OpenAIRE

    Poncin, Sylvie; Lengelé, Benoît; Colin, Idesbald; Gérard, Anne-Catherine

    2008-01-01

    Hypothyroidism, together with glandular atrophy, is the usual outcome of destructive autoimmune thyroiditis. The impairment in the thyroid function results either from cell destruction or from Th1 cytokine-induced alteration in hormonogenesis. Here, we investigated the impact of the local immune context on the thyroid function. We used two rat thyroid cell lines (PCCL3 and FRTL-5) and human thyrocytes incubated with IL-1alpha/interferon (IFN) gamma together with IL-4, a Th2 cytokine, or with ...

  20. IMBALANCE OF IMMUNOREGULATORY Th1- AND Th2-CYTOKINES IN PERSISTENT VIRAL INFECTIONS

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    I. O. Naslednikova

    2007-01-01

    Full Text Available Abstract. The article is considering certain features of immunopathogenesis exhibited in persistent viral infections, taking into account modern data and recently introduced immunological techniques. It has been revealed that a long-term persistence of hepatitis B and C viruses, tick-borne encephalitis, and herpes simplex is accompanied by deficient functioning in the T-cell compartment of immune system, and by markedly altered production of immunoregulatory cytokines in peripheral blood mononuclear leukocytes, mainly characterized by Th2 predominance.

  1. Cytokine and adhesion molecule expression evolves between the neutrophilic and lymphocytic phases of viral meningitis.

    Science.gov (United States)

    Makis, Alexandros; Shipway, David; Hatzimichael, Eleftheria; Galanakis, Emmanouil; Pshezhetskiy, Dmitry; Chaliasos, Nikolaos; Stebbing, Justin; Siamopoulou, Antigone

    2010-09-01

    Viral meningitis is characterized by cerebrospinal fluid (CSF) lymphocyte pleocytosis, although neutrophils may predominate in the early phase. The T helper 1 (Th1)/Th2 cytokine balance and expression of adhesion molecules seem to be involved in the CSF chemotaxis. We aimed to determine expression of cytokines and adhesion molecules in enteroviral meningitis. We investigated the serum and CSF levels of adhesion molecules (E-selectin, L-selectin, vascular cell adhesion molecule-1 [VCAM-1], and intracellular adhesion molecule-1 [ICAM-1]) and cytokines (interleukin-12 [IL-12] and IL-4) in 105 children during an outbreak of enteroviral meningitis. Diagnosis was confirmed with positive polymerase chain reaction (PCR) and/or serology for echovirus or Coxsackie virus, and matched with control subjects for clinical features but with negative PCR and/or serology. Apart from VCAM-1, the CSF levels of all investigated inflammatory molecules were significantly increased. In serum, sL-selectin and ICAM-1 levels were significantly higher than control subjects. Serum and CSF L-selectin, serum VCAM-1, and CSF IL-12 were all observed to be expressed in significantly higher levels in the neutrophil-dominant subgroup (72% had duration of symptoms 24 h). Serum and CSF ICAM-1 was found at significantly higher levels in the latter group. Evolving expression of adhesion molecules and cytokines indicates a shift from Th1 to Th2 immune responses as infection progresses.

  2. Regulatory role of pro-Th1 and pro-Th2 cytokines in modulating the activity of Th1 and Th2 cells when B cell and macrophages are used as antigen presenting cells

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    Agrewala Javed N

    2006-08-01

    Full Text Available Abstract Background Presence of antigen presenting cells, expression of costimulatory molecules, the strength of first signal and cytokine milieu are quite important in influencing the reactivation of differentiated Th1 and Th2 cells. Results In the present study, we have analyzed the concerted action of pro-Th1 and pro-Th2 cytokines in the presence of B cells, peritoneal and splenic macrophages as antigen presenting cells and varied concentration of first (anti-CD3 Ab and second (B7-1 transfectant signals on the proliferation and cytokine secretion by Th1 and Th2 cells. Interesting observations were made that IFN-γ significantly augmented the secretion of IL-4 by Th2 cells when either B cells or splenic or peritoneal macrophages were used as APC. Further, IFN-γ significantly inhibited the proliferation of Th1 cells only in the presence of peritoneal macrophages. We have also observed that B cells could significantly respond to cytokines to further enhance the proliferation and cytokine release by Th1 and Th2 cells. But not much effect on addition of exogenous cytokines IL-1, IL-4, IL-5, IL-12 was observed on the proliferation of Th1 and Th2 cells in the presence of macrophages. In contrast, both IFN-γ and IL-2 significantly enhanced the production of IL-4 and IL-5 respectively, by Th2 cells in presence of B cells, splenic and peritoneal macrophages. Another important observation was that the addition of B7-1 transfectants in the cultures, which were stimulated with low dose of anti-CD3 Ab significantly, enhanced the proliferation and cytokine secretion. Conclusion This study indicates involvement of different type of APCs, cytokine milieu, dose of first and second signals in a concerted manner in the outcome of the immune response. The significance of this study is that the immunization with antigen along with costimulatory molecules may significantly reduce the dose of antigen and can generate better immune response than antigen alone.

  3. Effect of murine exposure to gamma rays on the interplay between Th1 and Th2 lymphocytes.

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    Ghazy, Amany A; Abu El-Nazar, Salma Y; Ghoneim, Hossam E; Taha, Abdul-Rahman M; Abouelella, Amira M

    2015-01-01

    Gamma radiation radiotherapy is one of the widely used treatments for cancer. There is an accumulating evidence that adaptive immunity is significantly contributes to the efficacy of radiotherapy. This study is carried out to investigate the effect of gamma rays on the interplay between Th1/Th2 response, splenocyte lymphoproliferative response to polyclonal mitogenic activators and lymphocytic capacity to produce IL-12 and IL-10 in mice. Results showed that exposure of intact spleens to different doses of γ-rays (5, 10, 20 Gy) caused spontaneous and dose-dependent immune stimulation manifested by enhanced cell proliferation and elevated IL-12 production with decreased IL-10 release (i.e., Th1 bias). While exposure of splenocytes suspension to different doses of γ-rays (5, 10, 20 Gy) showed activation in splenocytes stimulated by PWM at 5 Gy then a state of conventional immune suppression that is characterized by being dose-dependent and is manifested by decreased cell proliferation and IL-12 release accompanied by increase in IL-10 production (i.e., Th2 bias). In addition, we investigated the exposure of whole murine bodies to different doses of γ-rays and found that the exposure to low dose γ-rays (0.2 Gy) caused a state of immune stimulation terminated by a remarkable tendency for immune suppression. Exposure to 5 or 10 Gy of γ-rays resulted in a state of immune stimulation (Th1 bias), but exposure to 20 Gy showed a standard state of immune suppression (Th2 bias). The results indicated that apparently we can control the immune response by controlling the dose of γ-rays.

  4. Targeting beta- and alpha-adrenergic receptors differentially shifts Th1, Th2, and inflammatory cytokine profiles in immune organs to attenuate adjuvant arthritis

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    Dianne eLorton

    2014-08-01

    Full Text Available The sympathetic nervous system (SNS regulates host defense responses and restores homeostasis. SNS-immune regulation is altered in rheumatoid arthritis (RA and rodent models of RA, characterized by nerve remodeling in immune organs and defective adrenergic receptor (AR signaling to immune cell targets that typically promotes or suppresses inflammation via α- and β2-AR activation, respectively, and indirectly drives humoral immunity by blocking Th1 cytokine secretion. Here, we investigate how β2-AR stimulation and/or α-AR blockade at disease onset affects disease pathology and cytokine profiles in relevant immune organs from male Lewis rats with adjuvant-induced arthritis (AA. Rats challenged to induce AA were treated with terbutaline (TERB, a β2-AR agonist (600 μg/kg/day and/or phentolamine (PHEN, an α-AR antagonist (5.0 mg/kg/day or vehicle from disease onset through severe disease. We report that in spleen, mesenteric (MLN and draining lymph node (DLN cells, TERB reduces proliferation, an effect independent of IL-2. TERB also fails to shift Th cytokines from a Th1 to Th2 profile in spleen and MLN (no effect on IFN-γ and DLN (greater IFN-γ cells. In splenocytes, TERB, PHEN and co-treatment (PT promotes an anti-inflammatory profile (greater IL-10 and lowers TNF-α (PT only. In DLN cells, drug treatments do not affect inflammatory profiles, except PT, which raised IL-10. In MLN cells, TERB or PHEN lowers MLN cell secretion of TNF-α or IL-10, respectively. Collectively, our findings indicate disrupted β2-AR, but not α-AR signaling in AA. Aberrant β2-AR signaling consequently derails the sympathetic regulation of lymphocyte expansion, Th cell differentiation, and inflammation in the spleen, DLNs and MLNs that is required for immune system homeostasis. Importantly, this study provides potential mechanisms through which reestablished balance between α- and β2-AR function in the immune system ameliorates inflammation and joint

  5. 27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun-Mi, E-mail: lala1647@hanmail.net [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Kim, Bo-Young, E-mail: kimboyoung@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Lee, Sae-A, E-mail: saeah486@nate.com [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Eo, Seong-Kug, E-mail: vetvirus@chonbuk.ac.kr [Laboratory of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Yun, Yungdae, E-mail: yunyung@ewha.ac.kr [Department of Life Science, Ewha Womans University, Seoul 120-750 (Korea, Republic of); Kim, Chi-Dae, E-mail: chidkim@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Kim, Koanhoi, E-mail: koanhoi@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of)

    2014-02-01

    Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of Th1 lymphocyte recruitment in a cholesterol-rich milieu. A high cholesterol diet resulted in enhanced expression of CCR5 ligands, including CCL3 and CCL4, but not of proatherogenic CXCR3 ligands, in atherosclerotic arteries of ApoE{sup −/−} mice. 27-Hydroxycholesterol and 7α-hydroxycholesterol, cholesterol oxides (oxysterols) detected in abundance in atherosclerotic lesions, greatly induced the transcription of CCL3 and CCL4 genes in addition to enhancing secretion of corresponding proteins by THP-1 monocytic cells. However, an identical or even higher concentration of cholesterol, 7β-hydroxycholesterol, and 7-ketocholsterol did not influence expression of these chemokines. Conditioned media containing the CCR5 ligands secreted from THP-1 cells induced migration of Jurkat T cells expressing CCR5, a characteristic chemokine receptor of Th1 cells, but not of Jurkat T cells that do not express CCR5. The migration of CCR5-expressing Jurkat T cells was abrogated in the presence of a CCR5-neutralizing antibody. 27-Hydroxycholesterol and 7α-hydroxycholesterol enhanced phosphorylation of Akt. Pharmacological inhibitors of phosphoinositide-3-kinase/Akt pathways blocked transcription as well as secretion of CCL3 and CCL4 in conjunction with attenuated migration of CCR5-expressing Jurkat T cells. This is the first report on the involvement of cholesterol oxides in migration of distinct subtype of T cells. We propose that 27-hydroxycholesterol and 7α-hydroxycholesterol can trigger a sequence of events that leads to recruitment of Th1 lymphocytes and phosphoinositide-3-kinase/Akt pathways play a major role in the process. - Graphical abstract: Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of

  6. Effects of combined immune therapy on survival and Th1/rh2 cytokine balance in rat orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    CAO Hui; LIU Hua; WU Zhi-yong

    2007-01-01

    Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.Methods The model of rat orthotopic liver transplantation was established by modified Kamada's technique.Recipients were divided into group A (control group): SD→SD; group B (group of rejection): SD→Wistar without any treatment; group C: SD→Wistar with CsA monotherapy from day 1 to day 5; and group D: SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.Results The survival period of recipients in groups A (>60 days) and D (>60 days) was significantly longer than that in group B (13.8±2.4 days). The serum levels of interleukin 2 (IL-2) and interferon y in group B were significantly higher than those in other groups; the level of tumor necrosis factor α was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P<0.05).Conclusions Combined immune therapy can prolong the survival of allografts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.

  7. Effects of Ginkgo Leaf Extract on Function of Dendritic Cells and Th1/Th2 Cytokines in Patients with Unstable Angina Pectoris

    Institute of Scientific and Technical Information of China (English)

    LI Da-zhu; SHARMA Ranjit; ZENG Qiu-tang

    2005-01-01

    Objective: To investigate the effects of Ginkgo leaf extract (GLE) on function of dendritic cells (DC) and Th1/Th2 cytokines in patients with unstable angina pectoris(UAP). Methods: Fifty-four patients with UAP were equally assigned into two groups, the treated group and the control group, both treated with conventional Western medicine, but with GLE given additionally to the treated group. Blood of all patients was taken before and 4 weeks after treatment to prepare the peripheral mononuclear cells, then which were incubated in the completed medium containing granulocyte-macrophage colony stimulatory factor (GMCSF) and interleukin-4 (IL-4) to induce mature DC. The expression of co-stimulating factor CD86 (B7-2) on the surface of DC was detected by flow cytometry, and the stimulating capacity of DC was determined by mixed lymphocyte reaction (MLR). The blood levels of cytokines, interferon-γ (IFN-γ), and IL-4, were analyzed by ELISA, and blood C-reactive protein (CRP) level by turbidimetry. Moreover, the direct effect of Ginkgolide B on CD86 expression on DC were also tested in vitro. Results: After treatment, CD86 expression on DC, the stimulating capacity of DC as well as levels of IFN-γ and CRP were lowered in both groups ( P<0.05 or P<0.01), but the changes were much more significant in the treated group than those in the control group. Ginkgolide B showed a direct inhibitory effect on the CD86 expression on DC. Conclusion: The inhibition of GLE on DC and thereby the suppression on inflammatory reaction may be one of the mechanisms of GLE in treating patients with UAP.

  8. The presence of non-segmental vitiligo modifies intracellular cytokine subsets in patients with chronic lymphocytic thyroiditis.

    Science.gov (United States)

    Santaguida, M G; Del Duca, S C; Virili, C; Gargano, L; Centanni, M

    2010-01-01

    Chronic lymphocytic thyroiditis and vitiligo often occur in association and seem to be characterized by a prevalent Th1-driven autoimmune process. The aim of this study is to analyze selected intracellular Τh1 and Th2 cytokines in patients with Hashimoto?s thyroiditis when associated with non-segmental vitiligo. We analyzed intracellular interleukin-2, interferon-gamma (Τh1) and interleukin-4 (Th2), in peripheral blood lymphocytes of 23 patients with isolated Hashimoto?s thyroiditis (group A) and of 11 patients with Hashimoto?s thyroiditis associated with non-segmental vitiligo (group B). Peripheral blood lymphocytes were stimulated and incubated with specific monoclonal antibodies. Intracellular cytokines were assayed by flow cytometric analysis. Interleukin-2 and interferon-gamma positive cells were increased in almost all patients but the median values were similar in patients with isolated Hashimoto?s thyroiditis and in those with concurrent vitiligo. In contrast, the number of patients with increased interleukin-4 positive cells was higher in patients with thyroiditis and vitiligo (9/11) than in those with isolated thyroiditis (2/23; plymphocytes characterize Hashimoto?s thyroiditis when associated with non-segmental vitiligo, suggesting a modified balance from highly prevalent Th1 to mixed Th1/Th2 subset.

  9. Oral Administration of p-Hydroxycinnamic Acid Attenuates Atopic Dermatitis by Downregulating Th1 and Th2 Cytokine Production and Keratinocyte Activation.

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    Hyun-Su Lee

    Full Text Available Atopic dermatitis (AD is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production.

  10. CYTOKINE RECEPTORS OF BLOOD LYMPHOCYTES IN CHILDREN WITH BRONCHIAL ASTHMA

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    I.A. Gromov

    2006-01-01

    Full Text Available Blood lymphocyte membrane receptors to IFNγ, IL 2, IL 4, IL 5, IL 8 and IL 10 have been investigated to assess cytokine sensitivity variations in children with asthma. Thirty children aged 5–17 with remission of atopic bronchial asthma ranging from mild to moderate persistent formed the study group. Ten children without any atopic disorders formed the group of controls. The flow cytometry with direct reaction of monoclonal antibodies to the mentioned above cytokine receptors has been used. An increased expression of IL 2 (due to high affinity CD122 subunit and IL 5 receptors has been registered in children with asthma, and so a numbers of cells bearing IL 4 and IL 8 receptors that has trended to be higher. At the same time, there has been a decrease of IFNγ receptor expression an a trend to lower expression of IL 10 receptor in these children.Key words: bronchial asthma, children, interferon-γ, interleukins.

  11. Cytokine profile and lymphocyte subsets in type 2 diabetes

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    C.O. Francisco

    2016-01-01

    Full Text Available Type 2 diabetes mellitus (T2D is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old with T2D and 20 nonsmoking men (49.4±7.6 years old who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05. The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01. In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

  12. 27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes.

    Science.gov (United States)

    Kim, Sun-Mi; Kim, Bo-Young; Lee, Sae-A; Eo, Seong-Kug; Yun, Yungdae; Kim, Chi-Dae; Kim, Koanhoi

    2014-02-01

    Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of Th1 lymphocyte recruitment in a cholesterol-rich milieu. A high cholesterol diet resulted in enhanced expression of CCR5 ligands, including CCL3 and CCL4, but not of proatherogenic CXCR3 ligands, in atherosclerotic arteries of ApoE(-/-) mice. 27-Hydroxycholesterol and 7α-hydroxycholesterol, cholesterol oxides (oxysterols) detected in abundance in atherosclerotic lesions, greatly induced the transcription of CCL3 and CCL4 genes in addition to enhancing secretion of corresponding proteins by THP-1 monocytic cells. However, an identical or even higher concentration of cholesterol, 7β-hydroxycholesterol, and 7-ketocholsterol did not influence expression of these chemokines. Conditioned media containing the CCR5 ligands secreted from THP-1 cells induced migration of Jurkat T cells expressing CCR5, a characteristic chemokine receptor of Th1 cells, but not of Jurkat T cells that do not express CCR5. The migration of CCR5-expressing Jurkat T cells was abrogated in the presence of a CCR5-neutralizing antibody. 27-Hydroxycholesterol and 7α-hydroxycholesterol enhanced phosphorylation of Akt. Pharmacological inhibitors of phosphoinositide-3-kinase/Akt pathways blocked transcription as well as secretion of CCL3 and CCL4 in conjunction with attenuated migration of CCR5-expressing Jurkat T cells. This is the first report on the involvement of cholesterol oxides in migration of distinct subtype of T cells. We propose that 27-hydroxycholesterol and 7α-hydroxycholesterol can trigger a sequence of events that leads to recruitment of Th1 lymphocytes and phosphoinositide-3-kinase/Akt pathways play a major role in the process.

  13. IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes.

    Science.gov (United States)

    Dong, Jun; Ivascu, Claudia; Chang, Hyun-Dong; Wu, Peihua; Angeli, Roberta; Maggi, Laura; Eckhardt, Florian; Tykocinski, Lars; Haefliger, Carolina; Möwes, Beate; Sieper, Jochen; Radbruch, Andreas; Annunziato, Francesco; Thiel, Andreas

    2007-08-15

    Epigenetic modifications, including DNA methylation, profoundly influence gene expression of CD4(+) Th-specific cells thereby shaping memory Th cell function. We demonstrate here a correlation between a lacking fixed potential of human memory Th cells to re-express the immunoregulatory cytokine gene IL10 and its DNA methylation status. Memory Th cells secreting IL-10 or IFN-gamma were directly isolated ex vivo from peripheral blood of healthy volunteers, and the DNA methylation status of IL10 and IFNG was assessed. Limited difference in methylation was found for the IL10 gene locus in IL-10-secreting Th cells, as compared with Th cells not secreting IL-10 isolated directly ex vivo or from in vitro-established human Th1 and Th2 clones. In contrast, in IFN-gamma(+) memory Th cells the promoter of the IFNG gene was hypomethylated, as compared with IFN-gamma-nonsecreting memory Th cells. In accordance with the lack of epigenetic memory, almost 90% of ex vivo-isolated IL-10-secreting Th cells lacked a functional memory for IL-10 re-expression after restimulation. Our data indicate that IL10 does not become epigenetically marked in human memory Th cells unlike effector cytokine genes such as IFNG. The exclusion of IL-10, but not effector cytokines, from the functional memory of human CD4(+) T lymphocytes ex vivo may reflect the need for appropriate regulation of IL-10 secretion, due to its potent immunoregulatory potential.

  14. The Relationship between the Antitumor Effect of the IL-12 Gene Therapy and the Expression of Th1 Cytokines in an HPV16-Positive Murine Tumor Model

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    Flor García Paz

    2014-01-01

    Full Text Available Objective. The goal of the present study was to investigate the effect of IL-12 expressed in plasmid on the Th1 cytokine profile in an experimental HPV16-positive murine tumor model and the association with the IL-12’s antitumor effect. Methods. Mice were injected with BMK-16/myc cells to establish HPV16-positive tumor and then pNGVL3-mIL-12 plasmid; pcDNA3 plasmid or PBS was injected directly into tumor site. The antitumor effect of the treatment was evaluated and the cytokines expression profile in each tumor tissue was analyzed. Results. Treatment with pNGVL3-mIL-12 plasmid had a significant antitumor effect, and a Th2-Th3-type cytokines prolife was detected in the murine tumor model with expression of the cytokines IL-10, IL-4, and TGF-β1. However, after the tumor was treated with three intratumoral injections of plasmid containing IL-12 cDNA, it showed a cytokine profile associated with Th1 with expression of IL-2, IL-12, and IFN-γ cytokines and reduced expression of IL-10, IL-4, and TGF-β1. Conclusions. The treatment with the IL-12 gene in the experimental HPV16-positive tumor model promoted the activation of the cellular immune response via expression of a Th1-type cytokine profile and was associated with the inhibition of tumor growth. Thus, IL-12 treatment represents a novel approach for gene therapy against cervical cancer.

  15. Febrile temperatures attenuate IL-1 beta release by inhibiting proteolytic processing of the proform and influence Th1/Th2 balance by favoring Th2 cytokines.

    Science.gov (United States)

    Boneberg, Eva-Maria; Hartung, Thomas

    2003-07-15

    We investigated possible feedback mechanisms of febrile temperatures on LPS- and staphylococcal enterotoxin B (SEB)-induced cytokine release in human whole blood. LPS-induced IL-1beta release was inhibited at temperatures >38 degrees C, whereas intracellular proIL-1beta formation as well as the release of other cytokines except IL-18 were only attenuated above 42 degrees C, indicating that febrile temperatures impair the proteolytic processing of proIL-1beta. This attenuated processing is not due to either heat inactivation of caspase-1 or structural changes in proIL-1beta produced at higher temperatures. Instead, we propose that febrile conditions change cytosolic compartmentation or trafficking, so that synthesized proIL-1beta cannot encounter caspase-1. Febrile temperatures also influenced Th1/Th2 cytokine balance. We observed a 3-fold increase in the Th2-cytokines IL-5 and IL-13 and a reduction to 15% of the Th1-cytokine IL-2 when SEB-stimulated whole blood was incubated at 40 degrees C compared with 37 degrees C. These results indicate that fever limits the production of the fever-inducing IL-1beta and also influences the adaptive immune response, favoring Th2 cytokine production.

  16. Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response in vitro in subjects with contact allergy to the respective metals.

    Science.gov (United States)

    Minang, J T; Areström, I; Troye-Blomberg, M; Lundeberg, L; Ahlborg, N

    2006-12-01

    Nickel (Ni), the main cause of contact allergy to metals, induces in vitro production of both Th1- and Th2-type cytokines in peripheral blood mononuclear cells (PBMC) from allergic subjects. Because the knowledge of the cellular immune response to other metals involved in contact allergy has been limited, we investigated the cytokine profile induced by Ni, cobalt (Co), chromium (Cr), palladium (Pd) and gold (Au) in PBMC from patients with patch test reactivity to the respective metals. PBMC from patients with patch test reactivity to Ni, Co, Cr, Au and/or Pd (n = 31) and non-allergic controls (n = 5) were stimulated in vitro with corresponding metal salts. Th1- [interleukin (IL)-2 and interferon (IFN)-gamma] and Th2- (IL-4 and IL-13) type cytokine responses were measured by enzyme-linked immunospot (ELISpot) and/or enzyme-linked immunosorbent assay (ELISA). All metals induced a mixed Th1- and Th2-type cytokine production in PBMC from individual patients with patch test reactivity to the corresponding metal, but not in control PBMC. Significantly higher responses in the patient versus controls were found for Cr (IL-2 and IL-13), Pd (IL-2 and IL-4), Au (IL-13 and IFN-gamma) (all P reactivities to metals, respectively, were matched by the in vitro reactivity. In conclusion, our data suggest that sensitization to Co, Cr, Pd and Au results in a cellular immune response of a character similar to the mixed Th1- and Th2-type cytokine profile shown previously to be induced by Ni.

  17. A differential interplay between the expression of Th1/Th2/Treg related cytokine genes in Teladorsagia circumcincta infected DRB1*1101 carrier lambs

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    Hassan Musa

    2011-03-01

    Full Text Available Abstract Substantial debate exists on whether the immune response between sheep resistant and susceptible to gastrointestinal nematodes can be differentiated into a Th1 and Th2 phenotype. The present study addresses the hypothesis that variation in resistance to Teladorsagia circumcincta between DRB1*1101 (associated with reduced faecal egg count and worm burden carriers and non-carriers is due to a differential interplay in the expression of Th1/Th2 and regulatory T (Treg related cytokine genes. Lambs from each genotype were either slaughtered at day 0 (un-infected control or infected with 3 × 104 Teladorsagia circumcincta L3 and slaughtered at 3, 7, 21, and 35 days later. Lambs carrying the DRB1*1101 allele had a significantly lower worm burden (P compared to the non-carriers. Abomasal mucosal cytokine gene expression was evaluated by quantitative real-time PCR and comparison made for time and genotype effects. The response generated varied through the course of infection and was affected by genotype. DRB1*1101 carriers had an up-regulated expression of the Th1-related cytokine genes (IL-1β, TNFα, and IFN-γ at day 3, but this was replaced by an up-regulated expression of Th2-related cytokine genes (IL-10 and IL-13 and Treg-related cytokine genes (IL-2RA-CD25, TGFα, TGFβ, Arg2, MIF and FOXP3 by day 7. Conversely, in the non-carriers these changes in gene expression were delayed until days 7 and 21 post infection (pi, respectively. It is concluded that resistance to Teladorsagia circumcincta in animals carrying the DRB1*1101 allele is influenced by an earlier interplay between Th1, Th2 and T regulatory immune response genes.

  18. A differential interplay between the expression of Th1/Th2/Treg related cytokine genes in Teladorsagia circumcincta infected DRB1*1101 carrier lambs.

    Science.gov (United States)

    Hassan, Musa; Hanrahan, James P; Good, Barbara; Mulcahy, Grace; Sweeney, Torres

    2011-03-08

    Substantial debate exists on whether the immune response between sheep resistant and susceptible to gastrointestinal nematodes can be differentiated into a Th1 and Th2 phenotype. The present study addresses the hypothesis that variation in resistance to Teladorsagia circumcincta between DRB1*1101 (associated with reduced faecal egg count and worm burden) carriers and non-carriers is due to a differential interplay in the expression of Th1/Th2 and regulatory T (Treg) related cytokine genes. Lambs from each genotype were either slaughtered at day 0 (un-infected control) or infected with 3 × 10(4) Teladorsagia circumcincta L3 and slaughtered at 3, 7, 21, and 35 days later. Lambs carrying the DRB1*1101 allele had a significantly lower worm burden (P < 0.05) compared to the non-carriers. Abomasal mucosal cytokine gene expression was evaluated by quantitative real-time PCR and comparison made for time and genotype effects. The response generated varied through the course of infection and was affected by genotype. DRB1*1101 carriers had an up-regulated expression of the Th1-related cytokine genes (IL-1β, TNFα, and IFN-γ) at day 3, but this was replaced by an up-regulated expression of Th2-related cytokine genes (IL-10 and IL-13) and Treg-related cytokine genes (IL-2RA-CD25, TGFα, TGFβ, Arg2, MIF and FOXP3) by day 7. Conversely, in the non-carriers these changes in gene expression were delayed until days 7 and 21 post infection (pi), respectively. It is concluded that resistance to Teladorsagia circumcincta in animals carrying the DRB1*1101 allele is influenced by an earlier interplay between Th1, Th2 and T regulatory immune response genes.

  19. Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

    Science.gov (United States)

    Ruiz-Extremera, Angeles; Muñoz-Gámez, José Antonio; Abril-Molina, Ana; Salmerón-Ruiz, María Angustias; Muñoz-de-Rueda, Paloma; Pavón-Castillero, Esther José; Quiles-Pérez, Rosa; Carazo, Angel; Gila, Ana; Jimenez-Ruiz, Sergio Manuel; Casado, Jorge; Martín, Ana Belén; Sanjuán-Núñez, Laura; Ocete-Hita, Esther; Viota, Julián López; León, Josefa; Salmerón, Javier

    2013-01-01

    This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; Ppost-delivery period (Pproduction. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

  20. Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

    Directory of Open Access Journals (Sweden)

    Angeles Ruiz-Extremera

    Full Text Available This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%, with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001 or as Type-B (34%, with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001 and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01. On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05 than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

  1. Th1/Th2细胞因子在小鼠真菌性角膜炎中的表达%Expression of Th1 and Th2 type cytokines in experimental keratomycosis

    Institute of Scientific and Technical Information of China (English)

    胡建章; 许建斌; 黄定国; 林秀丽; 朱学军; 韩晓丽; 徐国兴

    2010-01-01

    Objective To detect the expression of Th1 and Th2 type cytokines in a mouse model of Fusarium solani keratitis, and investigate the role of immune response in this disease. Methods A mouse model of Fusarium solani keratitis was established by epikeratophakia. On day 1, 3, 5, 7 after inoculation, the appearance of corneal ulcer was observed and infected corneas were subjected to histopathological analysis. Th1 (IFN-γ, IL-12) and Th2 (IL-4, IL-10) cytokines production in the cornea was analyzed by enzyme-linked immunosorbent assay (ELISA), and cytokine mRNA levels were measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). T-bet mRNA level were detect by RT-PCR. Results The infected cornea was characterized by severe inflammation, diffuse edema and opacity, and much neovascularization occurred on 5 days after inoculation. Histopathologic examination showed at 1 day and 3 days after inoculation, the limbus, corneas and anterior chamber had marked dense inflammatory cell infiltration, extensive stromal collagen destruction and edema. However, at 5 and 7 days, with a decrease of PMNs infiltration, significant neovascularization and uneven thickening and much fibrocytes could be seen in the stroma. Both Thl and Th2 cytokine production and mRNA expression in the corneas were detected, and the Th1 cytokine levels were much higher than Th2 cytokine. The ratio of IFN-γ/IL-4 reached to the peak at 3 days, then decreased gradually. There was positive correlation between T-bet mRNA expression and the ratio of IFN-γ/IL-4 (P <0.05). Conclusions In fungal keratitis, both the Th1 and Th2 responses are involved in regulating the anti-fungal immunity, but the Th1 response is dominant in the course. The power of anti-fungal immunity is rised to peak on day 3 after inoculation.%目的 通过检测Th1/Th2细胞因子在小鼠真菌性角膜炎中的表达水平,探讨机体免疫在该病发展中的作用. 方法应用角膜表层镜法建立Balb/c

  2. TH1 and TH2 cytokines dataset in insulin users with diabetes mellitus and newly diagnosed breast cancer

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    Zachary A.P. Wintrob

    2017-04-01

    Full Text Available Exogenous insulin use may interfere with the T helper cells’ cytokine production. This dataset presents the relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, the T-helper 1 and 2 produced cytokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between T-helper cytokines stratified by of insulin use and controls is also provided.

  3. Polysaccharide Nucleic Acid of Bacillus Calmette Guerin Modulates Th1/Th2 Cytokine Gene Expression in Lipopolysaccharide-Induced Mastitis in Rats

    Institute of Scientific and Technical Information of China (English)

    MIAO Jin-feng; ZHANG Yuan-shu; HUANG Guo-qing; MA Hai-tian; ZOU Si-xiang; ZHU Yu-min

    2009-01-01

    The aim of this study was to evaluate, in rats, the changes in the T helper type 1 (Th 1)/Th2 radio in mammary glands after an intramammary infusion of lipopolysaccharide (LPS) and to characterize the moderating effects of the polysaecharide nucleic acid of Bacillus Calraette Guerin (BCG-PSN) on the mammary gland. In the control group, the levels of IL-2 and INF-γ, mRNA expression increased, whereas IL-4 mRNA expression decreased after LPS challenge. As a consequence, the INF-γ/IL-4 mRNA ratio was significantly higher at 3, 6, and 9 h post-infusion (PI) compared to the control value (O h; P<0.01).BCG-PSN increased mRNA expression of both INF-γ' and IL-4 before infusion of LPS. LPS challenge significantly the reduced Th1/Th2 eytokine ratio due to Th1 cytokine IFN-γ suppression and Th2 cytokine IL-4 upregulation compared with the control group. A significant reduction ofN-acety1-β-D-glucosaminidase (NAGase) was observed at 24 h PI in the BCG-PSN treatment group compared to the control group (P<0.05). Thus, it was demonstrated that level of BCG-PSN might change the Th1/Th2 ratio mainly by enhancing the Th2 immune response. This is the first report of a Th1/Th2 change induced by coliform mastitis and characterization of the effect of BCG-PSN on mammary gland inflammation. This study makes a better understanding of the mechanisms of coliform mastitis and provides a putative novel strategy for the prevention and/or treatment of mastitis.

  4. Characterization and Clinical Implication of Th1/Th2/Th17 Cytokines Produced from Three-Dimensionally Cultured Tumor Tissues Resected from Breast Cancer Patients

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    Anna Kiyomi

    2015-08-01

    Full Text Available OBJECTIVES: Several cytokines secreted from breast cancer tissues are suggested to be related to disease prognosis. We examined Th1/Th2/Th17 cytokines produced from three-dimensionally cultured breast cancer tissues and related them with patient clinical profiles. METHODS: 21 tumor tissues and 9 normal tissues surgically resected from breast cancer patients were cultured in thermoreversible gelatin polymer–containing medium. Tissue growth and Th1/Th2/Th17 cytokine concentrations in the culture medium were analyzed and were related with hormone receptor expressions and patient clinical profiles. RESULTS: IL-6 and IL-10 were expressed highly in culture medium of both cancer and normal tissues. However, IFN-γ, TNF-α, IL-2, and IL-17A were not detected in the supernatant of the three-dimensionally cultured normal mammary gland and are seemed to be specific to breast cancer tissues. The growth abilities of hormone receptor–negative cancer tissues were significantly higher than those of receptor-positive tissues (P = 0.0383. Cancer tissues of stage ≥IIB patients expressed significantly higher TNF-α levels as compared with those of patients with stage Th1/Th2/Th17 cytokines. Hormone receptor–positive cancer tissues showed less growth ability. TNF-α is suggested to be a biomarker for the cancer stage.

  5. Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

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    Smeets Ruben L

    2012-03-01

    Full Text Available Abstract Background T lymphocytes are orchestrators of adaptive immunity. Naïve T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors. Results from these experiments were validated in a human experimental setting using whole blood and purified CD4+ Tcells. Results Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation induced a Th1 expression profile reflected by increased expression of T-bet, RUNX3, IL-2, and IFNγ, whereas calcium-independent activation via PMA/CD28 induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCθ are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCθ in both Th1 and Th2 development. Medial signaling via MAPkinases appeared to be less important in these pathways, since specific inhibitors of these kinases displayed a minor effect on gene expression. Translation towards a primary, whole blood setting and purified human CD4+ T cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific, Lck and PKCθ dependent IFNγ production, whereas PMA/CD28 induced Th2 specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3-mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation enhanced GATA3 mRNA expression in primary human CD4+ Tcells. Conclusions This study identifies stimulatory pathways and gene expression profiles for in vitro skewing of T helper cell

  6. Relationship between T-lymphocyte cytokine levels and sero-response to hepatitis B vaccines

    Institute of Scientific and Technical Information of China (English)

    Vijayakumar Velu; Shanmugam Saravanan; Subhadra Nandakumar; Esaki Muthu Shankar; Appasamy Vengatesan; Suresh Sakharam Jadhav; Prasad Suryakant Kulkarni; Sadras Panchatcharam Thyagarajan

    2008-01-01

    AIM: TO investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders.METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers.RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10 in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P=0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response.CONCLUSION: Our findings suggest that unresponsiveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.

  7. DMPD: Induction of proliferation and cytokine production in human T lymphocytes bylipopolysaccharide (LPS). [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11090938 Induction of proliferation and cytokine production in human T lymphocytes ... (.png) (.svg) (.html) (.csml) Show Induction of proliferation and cytokine production in human T lymphocyte...and cytokine production in human T lymphocytes bylipopolysaccharide (LPS). Authors Ulmer AJ, Flad H, Rietsch

  8. Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.

    Science.gov (United States)

    Tan, Xiahui; Khalil, Najwa; Tesarik, Candice; Vanapalli, Karunasri; Yaputra, Viki; Alkhouri, Hatem; Oliver, Brian G G; Armour, Carol L; Hughes, J Margaret

    2012-04-01

    In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.

  9. Quantificação das citocinas séricas Th1/Th2 por citometria de fluxo no linfoma de Hodgkin clássico Measurement of Th1/Th2 serum cytokines by flow cytometry in classical Hodgkin lymphoma

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    Adriana K. Mitelman

    2009-08-01

    Full Text Available O linfoma de Hodgkin clássico (LHC é uma neoplasia com distúrbio na produção de citocinas. Estudos demonstram que o padrão anormal das citocinas no linfonodo acometido pela lesão contribui não somente com a proliferação das células malignas H-RS, como também com o característico infiltrado hiper-reativo que compõe o tecido no LHC. Esta disfunção pode ser observada tanto no quadro clínico dos pacientes, como nas características histopatológicas: sintomas B, deficiência na resposta imune celular, bandas de colágeno e eosinofilia. As concentrações séricas das citocinas Th1 (IL-2, TNF, INF-γ e Th2 (IL-4, IL-5, IL-10 foram estudadas em 45 pacientes com LHC, ao diagnóstico, e em 34 doadores saudáveis, por citometria de fluxo (CBA - cytometric beads array. Houve aumento das concentrações das citocinas TNF (pClassical Hodgkin lymphoma (CHL is a malignancy with an abnormal or unbalanced secretion/production of cytokines, which might support the growth of H-RS cells, their surrounding reactive bystander cells and may be responsible for the typical clinical and histopathologic features of CHL: systemic B symptoms, an apparent defect in cell-mediated immune response, tumor fibrosis and eosinophilic infiltrate. Serum concentrations of IL-2, IL-4, IL5, IL-10, TNF and IFN-γ (Th1/Th2 were measured in 45 patients at diagnosis of classical Hodgkin lymphoma and in 34 healthy controls by cytometric beads array (CBA. Levels of TNF (p<0.01, INF-γ(p<0.01, IL-4 (p=0.01, IL-5 (p<0.01 e IL-10 (p<0.01 were significantly higher in patients compared to the control group. No difference was observed for IL-2 between the two groups. On correlating Th1/Th2 cytokine concentrations with clinical risk factors, elevated IL-10 (Th2 levels are associated with variables that suggest worse prognoses including III/IV stage (p=0.01, B-symptoms (p=0.04, hemoglobin < 10.5g/dL (p=0.01, lymphocytes < 600/mm³ (p=0.01 and according to the seven

  10. Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines.

    Science.gov (United States)

    Ibrahim, José-Noel; Jounblat, Rania; Delwail, Adriana; Abou-Ghoch, Joelle; Salem, Nabiha; Chouery, Eliane; Megarbane, André; Medlej-Hashim, Myrna; Lecron, Jean-Claude

    2014-10-01

    In order to clarify the inflammatory mechanism underlying familial Mediterranean fever (FMF), we aimed to evaluate the ex vivo cytokine profile of FMF patients during acute attacks and attack-free periods, and compare it with that of healthy controls. The study included 34 FMF patients, of whom 9 were studied during attack and remission and 24 healthy controls. Cytokine levels were evaluated by Luminex technology in serum and supernatants of PBMC (Peripheral Blood Mononuclear Cells) cultures with and without 24h stimulation of monocytes by LPS and T lymphocytes by anti-CD3/CD28 beads. Levels of IL-6 and TNF-α were higher in unstimulated and LPS-stimulated PBMC supernatants of FMF patients in crises compared to controls. In response to LPS stimulation, higher levels of IL-1β and IL-1α were found in PBMC supernatants of patients during crises compared to those in remission and to controls. IFN-γ and IL-4 levels were the lowest in unstimulated and anti-CD3/CD28 stimulated PBMCs supernatants of patients during crises compared to remission and controls. The Th17 cytokines IL-17 and IL-22 were respectively higher in anti-CD3/CD28 stimulated PBMC supernatants of FMF patients during and between crises compared to controls. Amongst cytokines tested in serum, only IL-6 and TNFα were enhanced in FMF patients. The ex vivo study represents an interesting approach to evaluate cytokines' involvement in FMF. Our results suggest an ongoing subclinical inflammation and define an elevated inflammatory cytokine signature, distinctly for M694V homozygous patients. The absence of spontaneous IL-1β release by PBMCs reflects no constitutive activation of the inflammasome in FMF physiopathology.

  11. Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2.

    Science.gov (United States)

    Demissie, Abebech; Abebe, Markos; Aseffa, Abraham; Rook, Graham; Fletcher, Helen; Zumla, Alimuddin; Weldingh, Karin; Brock, Inger; Andersen, Peter; Doherty, T Mark

    2004-06-01

    The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes "protective immunity" is one of the holy grails of M. tuberculosis immunology. It is known that IFN-gamma is essential for protection, but it is also apparent that IFN-gamma levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4delta2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response.

  12. Streptococcus pneumoniae fructose-1,6-bisphosphate aldolase, a protein vaccine candidate, elicits Th1/Th2/Th17-type cytokine responses in mice.

    Science.gov (United States)

    Elhaik Goldman, Shirin; Dotan, Shahar; Talias, Amir; Lilo, Amit; Azriel, Shalhevet; Malka, Itay; Portnoi, Maxim; Ohayon, Ariel; Kafka, Daniel; Ellis, Ronald; Elkabets, Moshe; Porgador, Angel; Levin, Ditza; Azhari, Rosa; Swiatlo, Edwin; Ling, Eduard; Feldman, Galia; Tal, Michael; Dagan, Ron; Mizrachi Nebenzahl, Yaffa

    2016-04-01

    Streptococcus pneumoniae (S. pneumoniae) is a major pathogen worldwide. The currently available polysaccharide-based vaccines significantly reduce morbidity and mortality. However, the inherent disadvantages of the currently available polysaccharide-based vaccines have motivated the search for other bacterial immunogens capable of eliciting a protective immune response against S. pneumoniae. Fructose-1,6-bisphosphate aldolase (FBA) is a glycolytic enzyme, which was found to localize to the bacterial surface, where it functions as an adhesin. Previously, immunizing mice with recombinant FBA (rFBA) in the presence of alum elicited a protective immune response against a lethal challenge with S. pneumoniae. Thus, the aim of the present study was to determine the cytokine responses that are indicative of protective immunity following immunization with rFBA. The protective effects against pneumococcal challenge in mice immunized with rFBA with complete Freund's adjuvant (CFA) in the initial immunization and with incomplete Freund's adjuvant (IFA) in booster immunizations surpassed the protective effects observed following immunization with either rFBA + alum or pVACfba. CD4+ T-cells obtained from the rFBA/CFA/IFA/IFA-immunized mice co-cultured with rFBA-pulsed antigen-presenting cells (APCs), exhibited a significantly greater proliferative ability than CD4+ T-cells obtained from the adjuvant-immunized mice co-cultured with rFBA‑pulsed APCs. The levels of the Th1-type cytokines, interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF)-α and IL-12, the Th2-type cytokines, IL-4, IL-5 and IL-10, and the Th17-type cytokine, IL-17A, significantly increased within 72 h of the initiation of co-culture with CD4+ T-cells obtained from the rFBA‑immunized mice, in comparison with the co-cultures with CD4+ T-cells obtained from the adjuvant-immunized mice. Immunizing mice with rFBA resulted in an IgG1/IgG2 ratio of 41, indicating a Th2 response with substantial Th1

  13. Pre-existing adenovirus immunity modifies a complex mixed Th1 and Th2 cytokine response to an Ad5/HIV-1 vaccine candidate in humans.

    Directory of Open Access Journals (Sweden)

    Samuel O Pine

    Full Text Available The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, ClinicalTrials.gov #NCT00849732. Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer ≤18; n = 36 or Ad5-seropositive (titer >200; n = 34. Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-γ, IL-2, TNF-α, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p<0.0001 for 9 out of 11 significantly expressed analytes. At the peak response time point, PBMC from Ad5-seronegative vaccinees secreted significantly more IP-10 in response to Gag (p = 0.008, and significantly more IP-10 (p = 0.0009, IL-2 (p = 0.006 and IL-10 (p = 0.05 in response to Ad5 empty vector than PBMC from Ad5-seropositive vaccinees. Additionally, similar responses to the Ad5 vector prior to vaccination were observed in almost all subjects, regardless of Ad5 neutralizing antibody status, and the levels of secreted IFN-γ, IL-10, IL-1Ra and GM-CSF were blunted following vaccination. The cytokine response profile of Gag-specific T cells mirrored the Ad5-specific response present in all subjects before vaccination, and included a number of Th1- and Th2-associated cytokines not routinely assessed in current vaccine trials, such as IP-10, IL-10, IL-13, and GM-CSF. Together, these

  14. Effect of IL-10 gene transmission on the PTg-stimulated splenocytes proliferation and Th1 cytokines production from experimental autoimminue thyroiditis rats

    Institute of Scientific and Technical Information of China (English)

    Wei Tang; Cuiping Liu; Youwen Qin; Yue Jia; Xiaodong Mao; Chao Liu

    2007-01-01

    Objective: To investigate the effects of gene therapy with IL-10 on PTg-induced proliferation of splenocytes and Th1 cytokine production from PTg-stimulated splenocytes. Methods: EAT rats were divided into four groups:group A (PBS+PLL) , group B (pORF+PLL), group C (pORFmIL10+PLL), and group D (pORFmIL10+ MEM). The substances mixed with lipofectamine were injected into the thyroid tissues of rats on the 18th dday after immunization. The rats were sacrificed at the 8th week. In vitro proliferative responses to ConA and different concentration of PTg were measured by culturing 4×105 splenocytes pulsed with 18.SKBq of [3H] thymidine for the final 12h and then harvested for liquid scintillation counting. In vitro splenocytes were cultured with PTg (25 mg/L). Th1 cytokine IFN-γ,TNF-αand IL-2 were detected by ELISA. Results: The proliferative response to PTg was suppressed in group C, compared with that of group A and B (P<0.05). The levels of IFN-γ,TNF-oand IL-2 in the supernatant of PTg-stimulated splenocytes were 3548.25 ± 779.47 pg/ml, 27.66±10.50 pg/ml and 3617.73± 609.15 pg/ml, respectively,which were much lower in group C than those in group A and B(P<0.01, P<0.05, P<0.001, respectively). Conclusion: IL-10 gene transmission in thyroid tissues could inhibit PTg specific proliferation of splenocytes from EAT rats and the secretion of Thl cytokines from PTg-stimulated splenocytes.

  15. Primary murine CD4+ T cells fail to acquire the ability to produce effector cytokines when active Ras is present during Th1/Th2 differentiation.

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    Sujit V Janardhan

    Full Text Available Constitutive Ras signaling has been shown to augment IL-2 production, reverse anergy, and functionally replace many aspects of CD28 co-stimulation in CD4+ T cells. These data raise the possibility that introduction of active Ras into primary T cells might result in improved functionality in pathologic situations of T cell dysfunction, such as cancer or chronic viral infection. To test the biologic effects of active Ras in primary T cells, CD4+ T cells from Coxsackie-Adenovirus Receptor Transgenic mice were transduced with an adenovirus encoding active Ras. As expected, active Ras augmented IL-2 production in naive CD4+ T cells. However, when cells were cultured for 4 days under conditions to promote effector cell differentiation, active Ras inhibited the ability of CD4+ T cells to acquire a Th1 or Th2 effector cytokine profile. This differentiation defect was not due to deficient STAT4 or STAT6 activation by IL-12 or IL-4, respectively, nor was it associated with deficient induction of T-bet and GATA-3 expression. Impaired effector cytokine production in active Ras-transduced cells was associated with deficient demethylation of the IL-4 gene locus. Our results indicate that, despite augmenting acute activation of naïve T cells, constitutive Ras signaling inhibits the ability of CD4+ T cells to properly differentiate into Th1/Th2 effector cytokine-producing cells, in part by interfering with epigenetic modification of effector gene loci. Alternative strategies to potentiate Ras pathway signaling in T cells in a more regulated fashion should be considered as a therapeutic approach to improve immune responses in vivo.

  16. Ribavirin and IFN-α combination therapy induces CD4+ T-cell proliferation and Th1 cytokine secretion in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the anti-viral mechanism of combination therapy of interferon (IFN)-α and ribavirin in patients with chronic hepatitis B.METHODS: Twenty patients were assigned to receive either IFN-α plus ribavirin (group A,n = 14) or no treatment as a control (group B,n = 6). Patients were analyzed for T-cell proliferative responses specific for hepatitis B virus (HBV)-antigen and cytokine production by peripheral blood mononuclear cells (PBMCs).RESULTS: Combination therapy induced HBV-antigen specific CD4+ T-cell proliferative responses in four patients (28.6%). Production of high levels of HBV-specific IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-12 by PBMCs was found in five patients (35.7%),who showed significantly lower HBV DNA levels in serum at 12 mo after treatment ended (P = 0.038) and at 24 mo of follow-up (P = 0.004) than those without high levels of cytokine production.CONCLUSION: HBV-antigen specific CD4+ T cells may directly control HBV replication and secretion of anti-viral T helper 1 (Th1) cytokines by PBMCs during combination therapy of chronic hepatitis B with ribavirin and IFN-α.

  17. Suppressed cytokine and immunoglobulin secretions by murine splenic lymphocytes infected in vitro with Toxoplasma gondii tachyzoites.

    Science.gov (United States)

    Guk, S M; Kook, J; Jeon, Y H; Choi, J H; Han, E T; Shin, E H; Chai, J Y

    2005-04-01

    Mechanisms of host immunosuppression after infection with Toxoplasma gondii are unclear. This study was performed to observe cytokine and immunoglobulin secretions by murine splenic lymphocytes infected in vitro with live, nonreplicating (irradiated) RH tachyzoites on stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS). For lymphocyte cultivation, 3 groups were prepared: coculture with live nonirradiated tachyzoites separated by a transwell (group T), live irradiated tachyzoites without a transwell (group R), and no tachyzoites (group C). Compared with group T, groups R and C, on stimulation with Con A, revealed significantly (P lymphocytes with T. gondii tachyzoites could impair their capacity to produce cytokine and immunoglobulin secretions.

  18. The increased but non-predominant expression of Th17- and Th1-specific cytokines in Hashimoto's thyroiditis but not in Graves' disease

    Science.gov (United States)

    Qin, Qiu; Liu, Ping; Liu, Lin; Wang, Rong; Yan, Ni; Yang, Jing; Wang, Xuan; Pandey, Madhu; Zhang, Jin-an

    2012-01-01

    Hashimoto's thyroiditis (HT) is considered to be mediated mainly by Th1 cells, but it is not known whether Graves' disease (GD) is associated with Th1 or Th2 predominance. Th17 cells, a novel subset of Th cells, play a crucial role in the pathogenesis of various autoimmune disorders. In the present study, the expression of IL-17A and IFN-γ was investigated in patients with HT or GD. mRNA expression of IL-17A and IFN-γ in peripheral blood mononuclear cells (PBMC) from 43 patients with autoimmune thyroid disease (AITD) and in thyroid tissues from 40 AITD patients were measured by real-time quantitative PCR. The protein expression of IL-17A and IL-23p19 was examined by immunohistochemistry in thyroid tissues from 28 AITD patients. The mRNA levels of IL-17A and IFN-γ were higher in both PBMC and thyroid tissues of HT patients than in controls (mRNA levels are reported as the cytokine/β-actin ratio: IL-17 = 13.58- and 2.88-fold change and IFN-γ = 16.54- and 2.74-fold change, respectively, P 0.05). The high protein expression of IL-17A (IOD = 15.17 ± 4.8) and IL-23p19 (IOD = 16.84 ± 7.87) in HT was confirmed by immunohistochemistry (P < 0.05). The similar high levels of IL-17A and IFN-γ suggest a mixed response of Th17 and Th1 in HT, where both cells may play important roles in the destruction procedure by cell-mediated cytotoxicity. PMID:23090124

  19. Elevated interleukin-27 enhances the polarization of Th1/Tc1 cells and the production of proinflammatory cytokines in primary immune thrombocytopenia.

    Science.gov (United States)

    Li, Hui Yuan; Zhang, Dong Lei; Ge, Jing; Zhou, Hu; Qi, Ai ping; Ma, Li; Xue, Feng; Zhou, Ze Ping; Yang, Ren Chi

    2012-03-01

    Primary immune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease with many immune dysfunctions. Interleukin-27 (IL-27) can regulate T cell differentiation. However, it is unclear whether IL-27 correlates with the dysfunctions of T cell differentiation in ITP patients. Thus, to determine the roles of IL-27 in ITP, we studied the expression of IL-27/IL-27 receptor in ITP patients. The results indicated that the levels of IL-27 in the plasma of untreated active ITP patients were higher than in normal controls. We next evaluated the contribution of IL-27 to T cell differentiation. Our results indicated that IL-27 increased T-bet expression, inhibited GATA-3 and ROR-γt expression, and promoted the secretion of tumor necrosis factor-α, interferon-γ, and granzyme B of peripheral blood mononuclear cells from ITP patients. Also, we confirmed that IL-27 induced the differentiation of T helper (Th)-1 and Tc1 cells. In conclusion, IL-27 might play an important role in the pathogenesis of ITP by inducing the polarization of Th1/Tc1 cells and the production of proinflammatory cytokines.

  20. Chronic lymphocytic leukemia cells diversify and differentiate in vivo via a nonclassical Th1-dependent, Bcl-6–deficient process

    Science.gov (United States)

    Patten, Piers E.M.; Ferrer, Gerardo; Chen, Shih-Shih; Simone, Rita; Marsilio, Sonia; Yan, Xiao-Jie; Gitto, Zachary; Yuan, Chaohui; Kolitz, Jonathan E.; Barrientos, Jacqueline; Allen, Steven L.; Rai, Kanti R.; MacCarthy, Thomas; Chu, Charles C.

    2016-01-01

    Xenografting primary tumor cells allows modeling of the heterogeneous natures of malignant diseases and the influences of the tissue microenvironment. Here, we demonstrate that xenografting primary chronic lymphocytic leukemia (CLL) B lymphocytes with activated autologous T cells into alymphoid mice results in considerable CLL B cell division and sizable T cell expansion. Nevertheless, most/all CD5+CD19+ cells are eventually lost, due in part to differentiation into antibody-secreting plasmablasts/plasma cells. CLL B cell differentiation is associated with isotype class switching and development of new IGHV-D-J mutations and occurs via an activation-induced deaminase-dependent pathway that upregulates IRF4 and Blimp-1 without appreciable levels of the expected Bcl-6. These processes were induced in IGHV-unmutated and IGHV-mutated clones by Th1-polarized T-bet+ T cells, not classical T follicular helper (Tfh) cells. Thus, the block in B cell maturation, defects in T cell action, and absence of antigen-receptor diversification, which are often cardinal characteristics of CLL, are not inherent but imposed by external signals and the microenvironment. Although these activities are not dominant features in human CLL, each occurs in tissue proliferation centers where the mechanisms responsible for clonal evolution operate. Thus, in this setting, CLL B cell diversification and differentiation develop by a nonclassical germinal center–like reaction that might reflect the cell of origin of this leukemia. PMID:27158669

  1. CD45-mediated signaling pathway is involved in Rhizoctonia bataticola lectin (RBL)-induced proliferation and Th1/Th2 cytokine secretion in human PBMC

    Energy Technology Data Exchange (ETDEWEB)

    Pujari, Radha [National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Eligar, Sachin M. [Department of Biochemistry, Karnatak University, Dharwad, 580003 Karnataka (India); Kumar, Natesh [National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Nagre, Nagaraja N.; Inamdar, Shashikala R.; Swamy, Bale M. [Department of Biochemistry, Karnatak University, Dharwad, 580003 Karnataka (India); Shastry, Padma, E-mail: padma@nccs.res.in [National Centre for Cell Science, Ganeshkhind, Pune 411007 (India)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer RBL, a potent mitogenic and complex N-glycan specific lectin binds to CD45 on PBMC. Black-Right-Pointing-Pointer RBL triggers CD45-mediated signaling involved in activation of p38MAPK and STAT-5. Black-Right-Pointing-Pointer Inhibition of CD45 PTPase signaling blocks RBL-induced ZAP70 phosphorylation. Black-Right-Pointing-Pointer RBL-CD45 mediated signaling is crucial for RBL-induced immunodulatory activities. -- Abstract: We earlier reported the mitogenic and immunostimulatory activities of Rhizoctonia bataticola lectin (RBL), purified from phytopathogenic fungus R. bataticola in human PBMC. The lectin demonstrates specificity towards glycoproteins containing complex N-glycans. Since CD45-protein tyrosine phosphatase that abundantly expresses N-glycans is important in T-cell signaling, the study aimed to investigate the involvement of CD45 in the immunomodulatory activities of RBL. Flowcytometry and confocal microscopy studies revealed that RBL exhibited binding to PBMC and colocalized with CD45. The binding was comparable in cells expressing different CD45 isoforms-RA, -RB and -RO. CD45 blocking antibody reduced the binding and proliferation of PBMC induced by RBL. CD45-PTPase inhibitor dephostatin inhibited RBL-induced proliferation, expression of CD25 and pZAP-70. RBL-induced secretion of Th1/Th2 cytokines were significantly inhibited in presence of dephostatin. Also, dephostatin blocked phosphorylation of p38MAPK and STAT-5 that was crucial for the biological functions of RBL. The study demonstrates the involvement of CD45-mediated signaling in RBL-induced PBMC proliferation and Th1/Th2 cytokine secretion through activation of p38MAPK and STAT-5.

  2. Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1 cytokines and reduces HBsAg level in transgenic mice

    Institute of Scientific and Technical Information of China (English)

    MENG Zhe-feng; WANG Hua-jing; YAO Xin; WANG Xuan-yi; WEN Yu-mei; DAI Jian-xin; XIE You-hua; XU Jian-qing

    2012-01-01

    Background The Fc receptor associated pathway might improve the immune responses against hepatitis B virus (HBV) as previously described by us.In addition,the Flt3 ligand (FL) has been reported to potentiate antigen presenting cells in vivo and may act as a potential adjuvant to boost antigen-specific immune responses.In this study,the immune efficacies of a set of fusion proteins of HBsAg and Fc and/or FL were evaluated in HBsAg transgenic mice.Methods The fusion proteins composed of HBsAg and the Fc domain of murine IgG1 (HBsAg-Fc) and/or the Flt3 ligand,and yeast-derived recombinant HBsAg were used as immunogen to immunize HBsAg transgenic mice,respectively.Serum and liver HBsAg levels,serum anti-HBsAg and cytokine profile,and the activities of alanine aminotransferase (ALT)/AST were investigated after immunization.Results After six injections,the most pronounced decrease in serum and liver HBsAg levels was observed in the HBsAg-Fc immunized group.In addition,serum Th1 cytokines and ALT/AST activities were highest in this group,indicating an effective induction of a favorable cellular immune response.Interestingly,the fusion protein containing HBsAg-Fc and the Flt3 ligand stimulated an alternative Th1-type immune response featured with high level productions of tumor necrosis factor α (TNF- α) and monocyte chemoabstractant protein 1 (MCP-1),causing a more severe cytotoxicity in hepatocytes while showed less effective in reducing serum HBsAg level.Conclusion HBsAg-Fc is effective in eliciting both the humoral and cellular immune responses against HBsAg in HBsAg transgenic mice,which makes it a potential immunogen for the immunotherapy of chronic hepatitis B.

  3. Caffeic acid phenethyl ester modifies the Th1/Th2 balance in ileal mucosa after γ-irradiation in the rat by modulating the cytokine pattern

    Institute of Scientific and Technical Information of China (English)

    Olivier Grémy; Marc Benderitter; Christine Linard

    2006-01-01

    AIM: To pharmacologically modulate Th polarization in the ileum exposed to ionizing radiation by using the immuno-modulatory/apoptotic properties of Caffeic Acid Phenethyl Ester (CAPE).METHODS: Rats received CAPE (30 mg/kg) treatment ip 15 min prior to intestinal 10 Gy γ-irradiation and once a day for a 6 d period after irradiation. Expression of genes implicated in Th differentiation in ileal mucosa (IL-23/IL12Rβ2), Th cytokine responses (IFN-γ, IL-2, IL-4, IL-13),Th migratory behaviour (CXCR3, CCR5, CCR4), Th signailing suppressors (SOCS1, SOCS3), transcription factor (T-Bet, GATA-3) and apoptosis (FasL/Fas, TNF/TNFR,XIAP, Bax, caspase-3) was analyzed by RT-PCR 6 h and 7 d post-irradiation. CD4+ and TUNEL positive cells were visualized by immunostaining.RESULTS: The expression of Th1-related cytokine/chemokine receptors (IFN-γ, IL-2, CXCR3, CCR5) was repressed at 7 d post-irradiation while Th2 cell cytokine/chemokines (IL-4, IL-13, CCR4) were not repressed or even upregulated. The irradiation-induced Th2 profile was confirmed by the upregulation of both Th2-specific transcription factor GATA-3 and SOCS3. Although an apoptosis event occurred 6 h after 10 Gy of intestinal γ-irradiation, apoptotic mediator analysis showed a tendency to apoptotic resistance 7 d post-irradiation. CAPE amplified apoptotic events at 6h and normalized Bax/FasL expressions at 7 d.CONCLUSION: CAPE prevented the ileal Th2 immune response by modulating the irradiation-influenced cytokine environment and apoptosis.

  4. T-bet/GATA-3 ratio is a surrogate measure of Th1/Th2 cytokine profiles and may be novel targets for CpG ODN treatment in asthma patients

    Institute of Scientific and Technical Information of China (English)

    DONG Liang; CHEN Ming; ZHANG Qi; LI Li-zheng; XU Xiao-qun; XIAO Wei

    2006-01-01

    @@ Naive helper T (Th) cells are divided into two subsets, Th1 and Th2. Th1 cells produce predominantly interferon-γ (IFN-γ), and Th2 cells produce interleukin-4 (IL-4), IL-5 and IL-13, but not IFN-γ.1 In asthma, an imbalance in the Th1/Th2 cytokine ratio characterized with a shift towards a predominantly Th2 cytokine profile in asthma occurs.2 The differentiation of naive helper T cells towards Th1 or Th2 cells is regulated by the ranscription factors T-box expressed in T-cells (T-bet) and GATA-binding protein-3 (GATA-3).3 We therefore hypothesized that the altered Th1/Th2cytokine expression in asthma is the result of a shift from T-bet to GATA-3 profile. In this study, we demonstrated that the ratio of T-bet/GATA-3 could predict the imbalance of Th1/Th2 cytokine in asthma patients.

  5. Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines.

    Science.gov (United States)

    Olleros, Maria L; Martin, Maria L; Vesin, Dominique; Fotio, Agathe L; Santiago-Raber, Marie-Laure; Rubbia-Brandt, Laura; Spahr, Laurent; Hadengue, Antoine; Garcia, Irene

    2008-10-01

    Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were analyzed. Endotoxin administration to either FAT-fed or FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice. Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice which presented the highest levels, but low levels were found in standard chow mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN-gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low-dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS. In this model, changes in the regulation of TNF are associated with increased expression of IL-6, IFN-gamma, and iNOS.

  6. Plasma Interleukin-37 Is Elevated in Patients with Rheumatoid Arthritis: Its Correlation with Disease Activity and Th1/Th2/Th17-Related Cytokines

    Directory of Open Access Journals (Sweden)

    Ting Xia

    2015-01-01

    Full Text Available Interleukin- (IL- 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28 and C-reactive protein (CRP, were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1β were analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28 and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA.

  7. Herbal medicine Gamgungtang down-regulates autoimmunity through induction of TH2 cytokine production by lymphocytes in experimental thyroiditis model.

    Science.gov (United States)

    Sa, Eun-Ho; Jin, Un-Ho; Kim, Dong-Soo; Kang, Bong-Seok; Ha, Ki-Tae; Kim, June-Ki; Park, Won-Hwan; Kim, Cheorl-Ho

    2007-02-12

    The crude herbal formulation, Gamgungtang (GGT), has been shown to protect animals against a wide range of spontaneously developing or induced autoimmune diseases. We have previously reported that GGT shows marked down-regulation of several experimental autoimmune diseases. Although very effective at preventing thyroid infiltrates in mice immunized with mouse deglycosylated thyroglobulin and complete Freund's adjuvant and in spontaneous models of thyroiditis, it completely failed to modify experimental autoimmune thyroiditis (EAT) induced in mice immunized with mouse thyroglobulin and lipopolysaccharide. In this study, in an effort to elucidate the mechanisms by which GGT suppresses EAT, and autoimmunity in general, we investigated the in vivo effects of this drug on the Th1/Th2 lymphocyte balance, which is important for the induction or inhibition of autoreactivity. Naive SJL/J mice were treated orally for 5 days with GGT (80 mg/(kg day)). Spleen cells were obtained at various time points during the treatment period and were stimulated in vitro with concanavalin A. Interleukins IL-4, IL-10 and IL-12, transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma) cytokine production was evaluated at the protein levels of the cytokines in the medium and mRNA expressions. A significant upregulation of IL-4, IL-10 and TGF-beta was observed following treatment with GGT, which peaked at day 5 (IL-10) or day 10 (IL-4). On the other hand, IL-12 and IFN-gamma production were either unchanged or decreased. It seems therefore that GGT induces in vivo a shift towards Th2 lymphocytes which may be one of the mechanisms of down-regulation of the autoimmune reactivity in EAT. Our observations indicate that down-regulation of TH1 cytokines (especially IL-12) and enhancement of Th2 cytokine production may play an important role in the control of T-cell-mediated autoimmunity. These data may contribute to the design of new immunomodulating treatments for a group of

  8. Th1/Th2型细胞因子对先兆流产的影响%Effect of Th1/Th2 Type Cytokines for Threatened Abortion

    Institute of Scientific and Technical Information of China (English)

    杜玉洁; 张大伟

    2016-01-01

    先兆流产的产生有50%为不明原因,现代医学把先兆流产的影响机制作为主要研究目标,根据近几年的研究结果显示,导致先兆流产的原因与T辅助细胞有关,其中T辅助细胞主要有Th1、Th2两型。本文将对近几年关于Th1/Th2对先兆流产的影响作一综述。%50%threatened abortion is caused by unknown reasons, modern medicine takes influence mechanism of threatened abortion as one of main research objects. Research result of recent years showed threatened abortion has relationship with T auxilliary cells, which include two types of Th1 and Th2 mainly. The article overviewed influence of Th1/Th2 on threatened abortion during recent years.

  9. Ma Huang Tang ameliorates asthma though modulation of Th1/Th2 cytokines and inhibition of Th17 cells in ovalbumin-sensitized mice.

    Science.gov (United States)

    Ma, Chun-Hua; Ma, Zhan-Qiang; Fu, Qiang; Ma, Shi-Ping

    2014-05-01

    Ma Huang Tang (Ephedra decoction, MHT) is a famous classical formula from Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects of MHT and the possible mechanisms were tested. An asthma model was established by ovalbumin (OVA)-induction in mice. A total of forty-eight mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg·kg(-1)) and MHT (5, 10, and 20 mg·kg(-1)). Airway resistance (Raw) was measured by the forced oscillation technique, histological studies were evaluated by hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th17 cells were evaluated by flow cytometry (FCM). This study demonstrated that MHT inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4 and IL-17 levels were recovered in bronchoalveolar lavage fluid, increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that MHT substantially inhibited Th17 cells. These findings suggest that MHT may effectively ameliorate the progression of asthma, and could be further investigated for potential use as a therapy for patients with allergic asthma. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  10. Immune effects of CpG-DNA and action of balancing Th1/Th2 cytokines secretion%胞嘧啶鸟嘌呤二核苷酸的免疫作用及调节Th1/Th2细胞因子的意义

    Institute of Scientific and Technical Information of China (English)

    黄维琳; 刘荣玉

    2008-01-01

    非甲基化的胞嘧啶鸟嘌呤二核苷酸(CpG DNA)可激活多种免疫效应细胞,诱导并增强天然和获得性免疫应答.CpG DNA具有免疫调节作用,能诱导Th1细胞因子产生,抑制Th2细胞因子的释放,并使Th2向Th1转变,其在疫苗佐剂、支气管哮喘、肿瘤的防治中有着广阔的应用前景.%Synthetic oligodeoxynucleoties containing unmethylated CpG motifs(CpG DNA) can trigger the activation of various immune cell subsets,induce and increase innate or acquired immune responses.CpG DNA can adjust immunity.It can induce Th1 cytokines and reduce Th2 cytOkines,and change Th2 cytokines into Th1 cytokines.CpG DNA has a widespread prospect in the immune adjuvants,therapy of asthma and tumor.

  11. Proinflammatory cytokines and their membrane-bound receptors are altered in the lymphocytes of schizophrenia patients.

    Science.gov (United States)

    Pandey, Ghanshyam N; Ren, Xinguo; Rizavi, Hooriyah S; Zhang, Hui

    2015-05-01

    Abnormalities of protein levels of proinflammatory cytokines and their soluble receptors have been reported in the plasma/serum of schizophrenia (SZ) patients. To examine if SZ is also associated with the abnormal gene expression of cytokines and their membrane-bound receptors, we studied mRNA expression of proinflammatory cytokines and their receptors in lymphocytes of SZ patients and normal control (NC) subjects. We determined the protein and mRNA expression of proinflammatory cytokines and mRNA expression of their receptors in lymphocytes from 30 SZ patients and 30 drug-free NC subjects. The subjects were diagnosed according to DSM-IV criteria. Protein levels of cytokines were determined by ELISA, and mRNA levels in lymphocytes were determined by the qPCR method. We found that the mRNA levels of IL-6, TNF-α, IL-1R1, TNFR1, and TNFR2, but not IL-1β, IL-1R2, IL-1RA, IL-6R, or GP130 were significantly increased in lymphocytes of SZ patients compared with NC subjects. We also found that the protein expression of IL-6 and TNF-α, but not IL-1β, was also significantly increased in SZ patients compared with NC subjects. These studies suggest that in addition to the reported abnormalities of proinflammatory cytokines and their soluble receptors in the plasma of SZ patients, an abnormal gene expression of these cytokines and their membrane-bound receptors may be involved in the pathogenesis of SZ.

  12. LYMPHOCYTE SUBSETS AND CYTOKINES IN BLOOD AND CEREBROSPINAL FLUID IN CHILDREN WITH VIRAL AND BACTERIAL MENINGITIS

    Directory of Open Access Journals (Sweden)

    L. A. Alekseeva

    2016-01-01

    Full Text Available Introduction of flow cytometry caused an increase in the investigation of liquor lymphocyte pool phenotype in the case of different brain disorders, including viral and bacterial meningitis, however this type of research in children has been relatively rare. Phenotype and lymphocyte functions are under cytokine control system, therefore detection of interconnections between lymphocyte pool subpopulation composition and cytokine level in blood and liquor of the patients concerns a great interest. The purpose of this research was to study lymphocyte subpopulation composition and the level of cytokines IL-1β, IL-6, IL-8, IL-10, IFNα, IFNγ and IL-4, and also IgG in liquor and blood of children with viral and bacterial meningitis. There was performed blood and liquor investigation in 46 children aged from 1 to 16 years old with viral (n = 35 and bacterial (n = 11 meningitis. Immunophenotyping of blood and liquor cells was performed by the method of flow cytometry with the use of monoclonal antibodies to CD3, CD4, CD8, CD19, CD16, CD56, CD25 and CD95. The content of cytokines was detected in ELISA, and that of IgG — by the method of quantitative immunoturbodimetry. During an acute period of viral meningitis there was detected a decrease in NK portion and activated CD25+ cells in the blood of patients accompanied by the increase in B-lymphocytes number, along with cytokine IFNγ, IL-8 and IL-10 serum level rise. There was determined T-lymphocytes accumulation in liquor with the prevalence of CD4+ Т-cells and, to a lesser degree, CD25+ and CD95+ cells, NK and B-lymphocytes. Intrathecally there was noted the predominance of IL-6 response accompanied by the growth of IL-8 and IL-10 concentration as well. During an acute period of bacterial meningitis there was noted a decrease in percentage of CD3+, CD4+, CD8+ Т-lymphocytes, NK, CD25+ and CD95+ cells, along with, on the contrary, sharp increase in B-cells pool, simultaneously with

  13. Relationship of thyroid ultrasound elasticity contrast index with serum autoantibody and Th1/Th2 cytokine levels in patients with Hashimoto's thyroiditis

    Institute of Scientific and Technical Information of China (English)

    Jian-Guo Sheng; Bin Wang; Kun-Kun Cao; Sai Zhang

    2016-01-01

    Objective:To study the relationship of thyroid ultrasound elasticity contrast index (ECI) with serum autoantibody and Th1/Th2 cytokine levels in patients with Hashimoto's thyroiditis. Methods:A total of 68 patients diagnosed with Hashimoto's thyroiditis (HT) in our hospitalas were selected as HT group, 60 healthy volunteers were selected as control group, ultrasound examination was performed to determine ECL, serum was collected to determine TPO-Ab, TG-Ab, IFN-γ, TNF-α, IL-2, IL-4 and IL-10 levels, and peripheral blood was collected to determine the positive expression rate of CD30 and CD195.Results:ECI of HT group was significantly higher than that of control group and the ECI of patients with small nodule type HT was significantly lower than that of patients with grid type HT; TPO-Ab, TG-Ab, IFN-γ, TNF-α and IL-2 levels in serum and positive expression rate of CD195 in peripheral blood of HT group were significantly higher than those of control group while IL-4 and IL-10 levels and positive expression rate of CD30 in peripheral blood were significantly lower than those of control group; TPO-Ab, TG-Ab, IFN-γ, TNF-α and IL-2 levels in serum and positive expression rate of CD195 in peripheral blood of patients with small nodule type HT were significantly lower than those of patients with grid type HT while IL-4 and IL-10 levels and positive expression rate of CD30 in peripheral blood were significantly higher than those of patients with grid type HT; ECI was positively correlated with TPO-Ab, TG-Ab, IFN-γ, TNF-α, IL-2b and CD195, and negatively correlated with IL-4, IL-10 and CD30.Conclusions:ECL significantly increases in patients with Hashimoto's thyroiditis and it can be used to evaluate the degree of immune dysfunction.

  14. Addition of exogenous cytokines in mixed lymphocyte culture for selecting related donors for bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Jeane Eliete Laguila Visentainer

    Full Text Available CONTEXT: Mixed lymphocyte culturing has led to conflicting opinions regarding the selection of donors for bone marrow transplantation. The association between a positive mixed lymphocyte culture and the development of graft-versus-host disease (GVHD is unclear. The use of exogenous cytokines in mixed lymphocyte cultures could be an alternative for increasing the sensitivity of culture tests. OBJECTIVE: To increase the sensitivity of mixed lymphocyte cultures between donor and recipient human leukocyte antigen (HLA identical siblings, using exogenous cytokines, in order to predict post-transplantation GVHD and/or rejection. TYPE OF STUDY: Prospective study. SETTING: Bone Marrow Transplantation Unit, Universidade Estadual de Campinas. PARTICIPANTS: Seventeen patients with hematological malignancies and their respective donors selected for bone marrow transplantation procedures. PROCEDURES: Standard and modified mixed lymphocyte culturing by cytokine supplementation was carried out using donor and recipient cells typed for HLA. MAIN MEASUREMENTS: Autologous and allogenic responses in mixed lymphocyte cultures after the addition of IL-4 or IL-2. RESULTS: In comparison with the standard method, average responses in the modified mixed lymphocyte cultures increased by a factor of 2.0 using IL-4 (p < 0.001 and 6.4 using IL-2 (p < 0.001, for autologous donor culture responses. For donor-versus-recipient culture responses, the increase was by a factor of 1.9 using IL-4 (p < 0.001 and 4.1 using IL-2 (p < 0.001. For donor-versus-unrelated culture responses, no significant increase was observed using IL-4, and a mean response inhibition of 20% was observed using IL-2 (p < 0.001. Neither of the cytokines produced a significant difference in the unrelated control versus recipient cell responses. CONCLUSION: IL-4 supplementation was the best for increasing the mixed lymphocyte culture sensitivity. However, IL-4 also increased autologous responses, albeit less

  15. IMMUNE AND CYTOKINE STATUS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA RECEIVING ALEMTUZUMAB

    Directory of Open Access Journals (Sweden)

    M. N Khorobrykh

    2010-01-01

    Full Text Available In present work, we studied cytokine levels and performed analysis of some immunologic parameters in the patients with chronic lymphocytic leukemia (CLL before and after treatment with monoclonal anti-CD52 antibody (alemtuzumab. In comparison with a control group, the CLL patients before alemtuzumab treatment showed a significant decrease in relative contents of CD3+ and CD4+ lymphocytes, CD4+/CD8+ T cells, diminished IFNγ and IL-4 levels, and a trend for TNFα increase. After ceasing the alemtuzumab treatment, the patients with CLL exhibited a significant decrease in absolute amounts of mature T-lymphocytes, CD4+, CD8+, CD20+ cells, as well as decreased relative contents of CD16+ lymphocytes. A sufficient post-treatment drop of serum IL-2 concentrations and a trend for serum TNFα and IFNγ decrease were also observed, as compared with pre-treatment values. The changes revealed may be connected with an additional immunosuppressive effect of alemtuzumab. The dynamics of cytokine levels and immunological parameters associated with alemtuzumab treatment is indicative for a weakening of cell-mediated immunity, thus resulting into a potential risk of infectious complications.

  16. 鼻息肉组织中Th1、Th2细胞因子的表达及其意义%Expression of Th1、Th2-typed cytokines and its significance in nasal polyps

    Institute of Scientific and Technical Information of China (English)

    李华斌; 许庚; 李源; 谢明强; 张革化

    2001-01-01

    目的:探讨IL-4、IL-5等8种细胞因子在鼻息肉发病中的作用和对鼻息肉治疗的意义。方法:采用酶联免疫吸附实验(ELISA)法检测25例鼻息肉患者鼻息肉组织中Th1细胞因子IFN-γ、IL-2、IL-12和Th2细胞因子IL-4、IL-5、IL-8、IL-10、IL-13的表达,并比较经皮质激素治疗前后鼻息肉中细胞因子表达的差异。结果:25例中,IL-4、IL-5、IL-8、IL-10、IL-13等Th2细胞因子的表达较正常组织增高,其中以IL-4、IL-5最为显著,分别达3.9倍和8.8倍;应用皮质激素后细胞因子的表达水平显著降低,而IFN-γ、IL-2、IL-12等Th1细胞因子浓度较正常组织中降低,应用激素后其表达无明显改变。结论:Th2细胞因子IL-4、IL-5、IL-8、IL-10、IL-13等的升高,在鼻息肉的发病过程中可能具有重要的意义,通过改变Th2细胞因子的表达趋势,可能对鼻息肉的治疗具有一定的意义。%Objective:To evaluate the possible role of cytokines in pathophysiology and treatment of nasal polyps.Method:The expressions of Th1-typed cytokines IFN-γ、IL-2 、IL-12 and Th2-typed cytokines IL-4、IL-5、IL-8、IL-10、IL-13 were investigated with enzyme-linked immune sorbent assay(ELISA) in 25 patients with nasal polyps.Result:There was a significant upregulation of Th2-typed cytokines IL-4、IL-5、IL-8、IL-10、IL-13 in nasal polyps compared with normal nasal mucosa, especially IL-4 and IL-5 (3.9 times and 8.8 times higher than normal mucous respectively) while the expression of Th1-typed cytokines IFN-γ、IL-2、IL-12 drcreased after treated with local glucocorticoid. The levels of Th2-typed cytokines decreased significantly and Th1-typed cytokines had no obvious change.Conclusion:The upregulation of Th2-typed cytokines such as IL-4、IL-5、IL-8、IL-10、IL-12 may play an important role in the pathophysiology of nasal polyps and Th2-typed cytokines can be viewed as a target of treatment to nasal polyps.

  17. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

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    Denise Silveira-Lemos

    2013-01-01

    Full Text Available Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group before and after praziquantel treatment (ACT-TR group. Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA, increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis.

  18. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

    Science.gov (United States)

    Silveira-Lemos, Denise; Fernandes Costa-Silva, Matheus; Cardoso de Oliveira Silveira, Amanda; Azevedo Batista, Mauricio; Alves Oliveira-Fraga, Lúcia; Soares Silveira, Alda Maria; Barbosa Alvarez, Maria Carolina; Martins-Filho, Olindo Assis; Gazzinelli, Giovanni; Corrêa-Oliveira, Rodrigo; Teixeira-Carvalho, Andréa

    2013-01-01

    Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis. PMID:23401741

  19. Myocardial Gene Expression of T-bet, GATA-3, Ror-γt, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-Type Response

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    Luciana Gabriel Nogueira

    2014-01-01

    Full Text Available Background. Chronic Chagas disease cardiomyopathy (CCC, a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC. Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13 or associated with Treg (TGF-β and IL-10 were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3+CTLA4+ Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.

  20. Expression pattern of transcription factors and intracellular cytokines reveals that clinically cured tuberculosis is accompanied by an increase in Mycobacterium-specific Th1, Th2, and Th17 cells.

    Science.gov (United States)

    da Silva, Marcos V; Massaro Junior, Vladimir J; Machado, Juliana R; Silva, Djalma A A; Castellano, Lúcio R; Alexandre, Patricia B D; Rodrigues, Denise B R; Rodrigues, Virmondes

    2015-01-01

    Tuberculosis (TB) remains a major global health problem and is the second biggest cause of death by infectious disease worldwide. Here, we investigate in vitro the Th1, Th2, Th17, and Treg cytokines and transcriptional factors produced after Mycobacterium-specific antigen stimulation in patients with active pulmonary tuberculosis, clinically cured pulmonary tuberculosis, and healthy donors with a positive tuberculin skin test (TST+). Together, our data indicate that clinical cure after treatment increases the percentages of Mycobacterium-specific Th1, Th2, and Th17 cells compared with those found in active-TB and TST+ healthy donors. These results show that the host-parasite equilibrium in latent TB breaks in favor of the microorganism and that the subsequent clinical recovery posttreatment does not return the percentage levels of such cells to those observed in latent tuberculosis. Additionally, our results indicate that rather than showing an increase in the percentage of Mycobacterium-specific Tregs, active-TB patients display lower Th1 : Treg and Th17 : Treg ratios. These data, together with lower Th1 : Th2 and Th17 : Th2 ratios, may indicate a mechanism by which the breakdown of the host-parasite equilibrium leads to active-TB and changes in the repertoire of Mycobacterium-specific Th cells that are associated with clinical cure after treatment of pulmonary tuberculosis.

  1. Expression Pattern of Transcription Factors and Intracellular Cytokines Reveals That Clinically Cured Tuberculosis Is Accompanied by an Increase in Mycobacterium-Specific Th1, Th2, and Th17 Cells

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    Marcos V. da Silva

    2015-01-01

    Full Text Available Tuberculosis (TB remains a major global health problem and is the second biggest cause of death by infectious disease worldwide. Here, we investigate in vitro the Th1, Th2, Th17, and Treg cytokines and transcriptional factors produced after Mycobacterium-specific antigen stimulation in patients with active pulmonary tuberculosis, clinically cured pulmonary tuberculosis, and healthy donors with a positive tuberculin skin test (TST+. Together, our data indicate that clinical cure after treatment increases the percentages of Mycobacterium-specific Th1, Th2, and Th17 cells compared with those found in active-TB and TST+ healthy donors. These results show that the host-parasite equilibrium in latent TB breaks in favor of the microorganism and that the subsequent clinical recovery posttreatment does not return the percentage levels of such cells to those observed in latent tuberculosis. Additionally, our results indicate that rather than showing an increase in the percentage of Mycobacterium-specific Tregs, active-TB patients display lower Th1 : Treg and Th17 : Treg ratios. These data, together with lower Th1 : Th2 and Th17 : Th2 ratios, may indicate a mechanism by which the breakdown of the host-parasite equilibrium leads to active-TB and changes in the repertoire of Mycobacterium-specific Th cells that are associated with clinical cure after treatment of pulmonary tuberculosis.

  2. Migration of Th1 lymphocytes is regulated by CD152 (CTLA-4-mediated signaling via PI3 kinase-dependent Akt activation.

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    Karin Knieke

    Full Text Available Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4 initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K-dependent activation of protein kinase B (PKB/Akt. In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response.

  3. Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection

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    McCall Matthew

    2010-06-01

    Full Text Available Abstract Background An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be influenced by micronutrient deficiencies. Methods Peripheral blood mononuclear cells from Tanzanian preschool children were stimulated in vitro with Plasmodium falciparum-parasitized red blood cells to determine T-cell responses to malaria under different conditions of nutrient deficiencies and malaria status. Results The data obtained indicate that zinc deficiency is associated with an increase in TNF response by 37%; 95% CI: 14% to 118% and IFN-γ response by 74%; 95% CI: 24% to 297%. Magnesium deficiency, on the other hand, was associated with an increase in production of IL-13 by 80%; 95% CI: 31% to 371% and a reduction in IFN-γ production. These results reflect a shift in cytokine profile to a more type I cytokine profile and cell-cell mediated responses in zinc deficiency and a type II response in magnesium deficiency. The data also reveal a non-specific decrease in cytokine production in children due to iron deficiency anaemia that is largely associated with malaria infection status. Conclusions The pathological sequels of malaria potentially depend more on the balance between type I and type II cytokine responses than on absolute suppression of these cytokines and this balance may be influenced by a combination of micronutrient deficiencies and malaria status.

  4. Th1/Th2 cytokine imbalance and the growth of cancer in S180 cancer-loaded rats under restriction stress%束缚应激条件下S180荷瘤小鼠Th1/Th2细胞因子失衡与肿瘤的生长

    Institute of Scientific and Technical Information of China (English)

    王济; 顾立刚; 彭桂英; 王庆国

    2005-01-01

    小鼠血清白细胞介素4和白细胞介素l0的含量明显增加.结论:束缚应激可显著抑制荷瘤小鼠的细胞免疫功能,使产生Thl型细胞因子的功能减弱,Th2型细胞因子的含量增加,导致Thl/Th2细胞的平衡进一步向Th2细胞漂移.这可能是其促进肿瘤生长的重要机制.%BACKGROUND: Restriction is a reliable means in the study of psychological stress, and restriction stress can suppress cellular immunity of T lymphocytes through hypothalamus-pituitary-adrenal axis.OBJECTIVE: To investigate the changes of Th1/Th2 balance due to restriction stress in cancer-loaded rats and the growth of cancer so as to explore the effect of psychological stress on cancer cells.DESIGN:Case control study based on experimental animal as subjects.SETTING: Teaching and Research Department of Microbiology and Immunology of Beijing University of Traditional Chinese Medical.MATERIALS: This study was carried out in the Immunology Laboratory of Beijing Traditional Chinese Medical University. Kunming rats of 6-8weeks old were selected. They were raised for 3 days before experiment to adapt to the environment and numbered according to their weight. Rats with the highest and lowest body weight were excluded, and the rest were randomly divided into 4 groups of 16 rats (8 male rats and 8 female rats)weighing 18 to 20 g.METHODS: S180 cancer cells were collected at 7 days of celiac subculture and rinsed with normal saline before made into cell suspensions of 1×1010 L-1 with RPMI 1640 medium. Rats were given subcutaneous injection of 0.2 mL cell suspension at the right axilla in cancer group and cancer-combined restriction group. Meanwhile, the same dosage of normal saline was used instead in normal control group and pure restriction group in the same way. After injection, movements of rats in pure restriction group and cancer-combined restriction group were restricted in specially-made tubes for 8 hours a day. Ten days later rats were killed to remove the tumor and thymus which

  5. Sulfasalazine and mesalamine modulate beryllium-specific lymphocyte proliferation and inflammatory cytokine production.

    Science.gov (United States)

    Dobis, Dave R; Sawyer, Richard T; Gillespie, May M; Newman, Lee S; Maier, Lisa A; Day, Brian J

    2010-10-01

    Occupational exposure to beryllium (Be) results in Be sensitization (BeS) that can progress to pulmonary granulomatous inflammation associated with chronic Be disease (CBD). Be-specific lymphocytes are present in the blood of patients with BeS and in the blood and lungs of patients with CBD. Sulfasalazine and its active metabolite, mesalamine, are clinically used to ameliorate chronic inflammation associated with inflammatory bowel disease. We tested whether sulfasalazine or mesalamine could decrease Be-stimulated peripheral blood mononuclear cell (PBMC) proliferation in subjects with CBD and BeS and Be-induced cytokine production in CBD bronchoalveolar lavage (BAL) cells. CBD (n = 25), BeS (n = 12) and healthy normal control (n = 6) subjects were enrolled and ex vivo proliferation and cytokine production were assessed in the presence of Be and sulfasalazine or mesalamine. Be-stimulated PBMC proliferation was inhibited by treatment with either sulfasalazine or mesalamine. Be-stimulated CBD BAL cell IFN-γ and TNF-α cytokine production was decreased by treatment with sulfasalazine or mesalamine. Our data suggest that both sulfasalazine and mesalamine interfere with Be-stimulated PBMC proliferation in CBD and BeS and dampens Be-stimulated CBD BAL cell proinflammatory cytokine production. These studies demonstrate that sulfasalazine and mesalamine can disrupt inflammatory pathways critical to the pathogenesis of chronic granulomatous inflammation in CBD, and may serve as novel therapy for human granulomatous lung diseases.

  6. Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Moser, Claus; Jensen, Peter Ø; Pressler, Tacjana;

    2005-01-01

    mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select subsets of dendritic cells, which subsequently induce distinct Th responses. Therefore, the present study examines the correlation between the mobilizing cytokines in serum and the Th responses. The IFN-gamma and IL-4...... lung function. In addition, an inverse correlation between IL-3 and IFN-gamma was observed. The results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed Th response in CF, and change to a Th1-dominated response might be achieved with GM-CSF treatment....

  7. Salidroside attenuates concanavalin A-induced hepatitis via modulating cytokines secretion and lymphocyte migration in mice.

    Science.gov (United States)

    Hu, Baoji; Zou, Yun; Liu, Shanshan; Wang, Jun; Zhu, Jiali; Li, Jinbao; Bo, Lulong; Deng, Xiaoming

    2014-01-01

    Salidroside, isolated from the medicinal plant Rhodiola, was reported to serve as an "adaptogen." This study was designed to explore the protective effect of salidroside on concanavalin A- (Con A-) induced hepatitis in mice and investigate potential mechanisms. C57BL/6 mice were randomly divided into control group, Con A group, and salidroside group. Salidroside (50 mg/kg) was injected intravenously followed by Con A administration. The levels of ALT, AST, inflammatory cytokines and CXCL-10 were examined. The pathological damage of livers was assessed, the amounts of phosphorylated IκBα and p65 were measured, and the numbers of CD4(+) and CD8(+) T lymphocytes in the blood, spleen and infiltrated in the liver were calculated. Our results showed that salidroside pretreatment reduced the levels of ALT, AST dramatically and suppressed the secretion of proinflammatory cytokines through downregulating the activity of NF-κB partly. Salidroside altered the distribution of CD4(+) and CD8(+) T lymphocyte in the liver and spleen through regulating CXCL-10 and decreased the severity of liver injuries. In conclusion, these results confirm the efficacy of salidroside in the prevention of immune mediated hepatitis in mice.

  8. Salidroside Attenuates Concanavalin A-Induced Hepatitis via Modulating Cytokines Secretion and Lymphocyte Migration in Mice

    Directory of Open Access Journals (Sweden)

    Baoji Hu

    2014-01-01

    Full Text Available Salidroside, isolated from the medicinal plant Rhodiola, was reported to serve as an “adaptogen.” This study was designed to explore the protective effect of salidroside on concanavalin A- (Con A- induced hepatitis in mice and investigate potential mechanisms. C57BL/6 mice were randomly divided into control group, Con A group, and salidroside group. Salidroside (50 mg/kg was injected intravenously followed by Con A administration. The levels of ALT, AST, inflammatory cytokines and CXCL-10 were examined. The pathological damage of livers was assessed, the amounts of phosphorylated IκBα and p65 were measured, and the numbers of CD4+ and CD8+ T lymphocytes in the blood, spleen and infiltrated in the liver were calculated. Our results showed that salidroside pretreatment reduced the levels of ALT, AST dramatically and suppressed the secretion of proinflammatory cytokines through downregulating the activity of NF-κB partly. Salidroside altered the distribution of CD4+ and CD8+ T lymphocyte in the liver and spleen through regulating CXCL-10 and decreased the severity of liver injuries. In conclusion, these results confirm the efficacy of salidroside in the prevention of immune mediated hepatitis in mice.

  9. 老年湿疹患者 Th 1/Th2细胞因子的血清水平与湿疹的发展及其临床表现的相关性%Serum levels of Th1/Th2 cytokines in aged patients and their correlation with eczema devel-opment and cl inical manifestation

    Institute of Scientific and Technical Information of China (English)

    汪为刚; 侯枫林; 张秀明; 马世武; 陈金军

    2016-01-01

    Objective:To investigate variations of Th1/Th2 cytokine levels,as well as their correlation with eczema de-velopment and clinical manifestation in aged patients.Methods:A total of 92 patients (above 60 years old)with eczema diag-nosed by the outpatient department of dermatology and venerology of our hospital were included as the eczema group,while 60 aged patients without eczema as the healthy group.Patients'serum levels of Th1/Th2 cytokines were examined for inter-group comparison and stratified analysis as per clinical manifestation.Results:Serum levels of interleukin (IL)-2,IL-4,IL-10,IL-12,tumor necrosis factor (TNF)-ɑand interferon (IFN)-γwere all significantly higher in patients of the eczema group than the healthy group (P 0.05).And no significant difference existed in the levels of IL-2,IL-4, IL-10,IL-12,TNF-ɑand IFN-γbetween generalized and localized eczema patients (P >0.05).Conclusion:Compared with the healthy population,Th1/Th2 cytokine levels are significantly different in eczema patients,especially those in the acute stage.%目的::研究分析老年湿疹患者 Th1/Th2细胞因子的水平变化与患者疾病发展及临床表现的关系.方法:选取本院皮肤性病门诊确诊的60岁以上的老年人92例(湿疹组)和60例健康老年人(健康组)作为研究对象,检测两组血清 Th1/Th2细胞因子水平并进行比较,并根据患者临床表现进行分层分析.结果:湿疹组患者的 IL-2、IL-4、IL-10、IL-12、TNF-ɑ、IFN-γ水平均显著的高于健康组人群且差异均具有统计学意义(P <0.05);湿疹组急性期患者的 IL-2、IL-4、IL-10、IFN-γ水平均显著的高于健康组人群且差异均具有统计学意义(P <0.05);急性期与慢性期湿疹患者的 IL-12、TNF-ɑ水平差异无统计学意义(P >0.05).湿疹组患者泛发性和局限性的 IL-2、IL-4、IL-10、IL-12、TNF-ɑ、IFN-γ水平均差异均不具有统计学意义(P >0.05).结论:湿疹患者的 Th

  10. 308nm准分子激光治疗对白癜风患者外周血Th1及Th2细胞因子的影响%Effect of 308nm excimer laser therapy on Th1/Th2 cytokines in peripheral blood of patients with vitiligo

    Institute of Scientific and Technical Information of China (English)

    李建英; 刘津民; 曹海育; 张玉红; 刘英权

    2014-01-01

    Objective To study the level of Th1 cytokine(IFN-γ) and Th2 cytokine (IL-4) in peripher-al blood of patients with vitiligo , and to explore the possible immune mechanism of 308 nm excimer laser for vitiligo therapy.Methods 50 cases of vitiligo were treated by 308nm excimer laser therapy , twice a week for 24 times.The level of IFN-γand IL-4 in peripheral blood from 50 vitiligo patients before and after treatment and 20 healthy per-son in control group were measured by enzyme linked immunosorbent assay .Results There was no difference be-tween two groups on the level of IL -4 (P>0.05).The level of IFN-γin vitiligo patients was higher than that in the control group (P0.05). Conclusion Th1 cytokine take advantage of vitiligo patients and involved in the pathogenesis of vitiligo .308nm ex-cimer laser therapy can restore the Th 1/Th2 balance .%目的:研究308 nm准分子激光对白癜风患者外周血Th1型细胞因子干扰素γ( IFN-γ)和Th2型细胞因子白细胞介素-4( IL-4)水平的影响,探讨其可能的作用机制。方法50例白癜风患者均采用308 nm准分子激光治疗,每周2次共治疗24次。采用酶联免疫吸附法( ELISA法)检测50例白癜风患者治疗前、后及20例正常健康者外周血IFN-γ及IL-4的水平,并统计临床疗效。结果治疗组治疗前IFN-γ水平较正常对照组升高,比较差异有统计学意义(P<0.05);治疗后较治疗前明显降低(P<0.05),且与正常对照组比较差异无统计学意义(P>0.05)。治疗组治疗前IL-4水平与正常对照组及本组治疗后比较差异均无统计学意义( P>0.05)。结论白癜风患者体内Th1型细胞因子占优势,308 nm准分子激光可恢复白癜风患者Th1及Th2的平衡状态。

  11. Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Nielsen, C H; Hegedüs, L; Rieneck, K;

    2007-01-01

    Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral bloo......-gamma, IL-5 and IL-10 responses were markedly inhibited by partial denaturation of Tg by boiling. We hypothesize that autoantibodies and complement may promote mixed Th1/Th2 cell cytokine responses by enhancing the uptake of autoantigens by antigen-presenting cells....... appeared to promote the production of IL-2 and particularly IL-5, the levels of which were reduced by neutralization of complement by heat- or zymosan treatment. The production of IFN-gamma and IL-2 of the three groups together correlated directly with the serum anti-Tg activity. Moreover, TNF-alpha, IFN...

  12. Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Hegedüs, L; Rieneck, Klaus

    2007-01-01

    Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral bloo......-gamma, IL-5 and IL-10 responses were markedly inhibited by partial denaturation of Tg by boiling. We hypothesize that autoantibodies and complement may promote mixed Th1/Th2 cell cytokine responses by enhancing the uptake of autoantigens by antigen-presenting cells...... appeared to promote the production of IL-2 and particularly IL-5, the levels of which were reduced by neutralization of complement by heat- or zymosan treatment. The production of IFN-gamma and IL-2 of the three groups together correlated directly with the serum anti-Tg activity. Moreover, TNF-alpha, IFN...

  13. Imbalanced shift of cytokine expression between T helper 1 and T helper 2 (Th1/Th2) in intestinal mucosa of patients with post-infectious irritable bowel syndrome.

    Science.gov (United States)

    Chen, Ji; Zhang, Yangde; Deng, Zhansheng

    2012-07-20

    Irritable bowel syndrome (IBS) is a common functional bowel disorder. The post-infectious IBS (PI-IBS) occurs in IBS patients with a history of intestinal infection preceding the onset of symptoms. However, the underlying cause of PI-IBS is not fully understood, and the purpose of this study was to investigate the immune regulatory mechanism of PI-IBS. Participants enrolled in this study were divided into three groups including PI-IBS patients (n = 20), IBS patients without a history of infection (non-PI-IBS, n = 18), and healthy controls (n = 20). The expression levels of the Th1-derived cytokines IFN-γ and IL-12, and the Th2-derived cytokines IL-4 and IL-10 in the mucosal specimens, and in the ascending colon, the descending colon, and the rectal segments were measured by RT-PCR and western blot. The IFN-γ mRNA levels in the intestinal mucosa were significantly higher in the PI-IBS group than in the non-PI-IBS or control group (both P colon, the descending colon, and the rectum of all groups. An increase in IFN-γ levels and a decrease in IL-10 levels were found in the intestinal mucosa of PI-IBS patients, suggesting that the infection may affect the Th1/Th2 balance. Thus, the dysregulation of the immune response is likely an important cause of IBS.

  14. Imbalanced shift of cytokine expression between T helper 1 and T helper 2 (Th1/Th2 in intestinal mucosa of patients with post-infectious irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Chen Ji

    2012-07-01

    Full Text Available Abstract Background Irritable bowel syndrome (IBS is a common functional bowel disorder. The post-infectious IBS (PI-IBS occurs in IBS patients with a history of intestinal infection preceding the onset of symptoms. However, the underlying cause of PI-IBS is not fully understood, and the purpose of this study was to investigate the immune regulatory mechanism of PI-IBS. Methods Participants enrolled in this study were divided into three groups including PI-IBS patients (n = 20, IBS patients without a history of infection (non-PI-IBS, n = 18, and healthy controls (n = 20. The expression levels of the Th1-derived cytokines IFN-γ and IL-12, and the Th2-derived cytokines IL-4 and IL-10 in the mucosal specimens, and in the ascending colon, the descending colon, and the rectal segments were measured by RT-PCR and western blot. Results The IFN-γ mRNA levels in the intestinal mucosa were significantly higher in the PI-IBS group than in the non-PI-IBS or control group (both P  Conclusions An increase in IFN-γ levels and a decrease in IL-10 levels were found in the intestinal mucosa of PI-IBS patients, suggesting that the infection may affect the Th1/Th2 balance. Thus, the dysregulation of the immune response is likely an important cause of IBS.

  15. Combined effects of circulating levels of 25-hydroxyvitamin d and Th1 and th2 cytokines on breast cancer estrogen receptor status.

    Science.gov (United States)

    Yao, Song; Hong, Chi-Chen; McCann, Susan E; Zirpoli, Gary; Quan, Lei; Gong, Zhihong; Johnson, Candace S; Trump, Donald L; Ambrosone, Christine B

    2014-01-27

    Vitamin D has been recognized for its immune-modulating properties. We have previously found that levels of 25OHD, and cytokines including IL5, IFNα2, and TNFα, are also associated with estrogen receptor (ER) negative breast cancer in younger women. Thus, we hypothesized that there may be interactions between vitamin D and the immune system in influencing breast cancer ER status, which was tested in 490 women with incident breast cancer. There was no correlation of the levels of 25OHD with any cytokine, and their associations with tumor ER negative status were independent of each other. However, premenopausal women with low 25OHD and high TNFα levels had the highest likelihood of having ER negative cancer (odds ratio [OR] = 7.32, 95% confidence interval [CI] = 2.44-21.98), with evidence of synergy between the two (relative excess risk due to interaction [RERI] = 5.46, p for additive interaction = 0.14, and p for multiplicative interaction = 0.09). There were similar synergistic associations between 25OHD and IL5, and several IFNα2 to Th2 cytokine ratios. This is the first study to provide evidence of interactions between vitamin D and the immune system in relation to breast cancer ER status, which may inform combinational use of vitamin D and anti-inflammatory drugs for cancer prevention and therapy.

  16. Combined Effects of Circulating Levels of 25-Hydroxyvitamin D and Th1 and Th2 Cytokines on Breast Cancer Estrogen Receptor Status

    Directory of Open Access Journals (Sweden)

    Song Yao

    2014-01-01

    Full Text Available Vitamin D has been recognized for its immune-modulating properties. We have previously found that levels of 25OHD, and cytokines including IL5, IFNα2, and TNFα, are also associated with estrogen receptor (ER negative breast cancer in younger women. Thus, we hypothesized that there may be interactions between vitamin D and the immune system in influencing breast cancer ER status, which was tested in 490 women with incident breast cancer. There was no correlation of the levels of 25OHD with any cytokine, and their associations with tumor ER negative status were independent of each other. However, premenopausal women with low 25OHD and high TNFα levels had the highest likelihood of having ER negative cancer (odds ratio [OR] = 7.32, 95% confidence interval [CI] = 2.44−21.98, with evidence of synergy between the two (relative excess risk due to interaction [RERI] = 5.46, p for additive interaction = 0.14, and p for multiplicative interaction = 0.09. There were similar synergistic associations between 25OHD and IL5, and several IFNα2 to Th2 cytokine ratios. This is the first study to provide evidence of interactions between vitamin D and the immune system in relation to breast cancer ER status, which may inform combinational use of vitamin D and anti-inflammatory drugs for cancer prevention and therapy.

  17. Correlation between the induction of Th1 cytokines by an attenuated equine infectious anemia virus vaccine and protection against disease progression.

    Science.gov (United States)

    Zhang, Xiaoyan; Wang, Ying; Liang, Hua; Wei, Li; Xiang, Wenhua; Shen, Rongxian; Shao, Yiming

    2007-03-01

    The equine infectious anemia virus (EIAV) donkey-leukocyte attenuated vaccine (DLV) has been used to protect against equine infectious anaemia (EIA) disease for several decades in China. The attenuated mechanism and immunological protective mechanisms remain to be elucidated. To identify responses that correlate with the protection against disease, we immunized horses with DLV, followed by challenge with an EIAV wild-type strain LN. All vaccinated horses were asymptomatic and had a low level of virus replication (10(7) copies ml-1) and intermittent febrile episodes. Cytokine production in the DLV-vaccinated horses increased and attained a plateau level at approximately 50 days post-vaccination, and exceeded 10(7) copies per 10(7) peripheral blood mononuclear cells (PBMCs) 1-3 months post-challenge. However, non-vaccinated control horses died after several fever episodes (>or=39 degrees C), which coincided with higher viral load (10(6)-10(7) copies ml-1) and lower cytokine production (<10(4) copies per 10(7) PBMCs). The results indicate that high levels of EIAV-specific cytokines induced by the attenuated EIAV vaccine may contribute to the protective immune response against EIA disease.

  18. Combined Effects of Circulating Levels of 25-Hydroxyvitamin D and Th1 and Th2 Cytokines on Breast Cancer Estrogen Receptor Status

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Song, E-mail: song.yao@roswellpark.org; Hong, Chi-Chen; McCann, Susan E.; Zirpoli, Gary; Quan, Lei; Gong, Zhihong [Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Johnson, Candace S. [Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Trump, Donald L. [Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Ambrosone, Christine B. [Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States)

    2014-01-27

    Vitamin D has been recognized for its immune-modulating properties. We have previously found that levels of 25OHD, and cytokines including IL5, IFNα2, and TNFα, are also associated with estrogen receptor (ER) negative breast cancer in younger women. Thus, we hypothesized that there may be interactions between vitamin D and the immune system in influencing breast cancer ER status, which was tested in 490 women with incident breast cancer. There was no correlation of the levels of 25OHD with any cytokine, and their associations with tumor ER negative status were independent of each other. However, premenopausal women with low 25OHD and high TNFα levels had the highest likelihood of having ER negative cancer (odds ratio [OR] = 7.32, 95% confidence interval [CI] = 2.44−21.98), with evidence of synergy between the two (relative excess risk due to interaction [RERI] = 5.46, p for additive interaction = 0.14, and p for multiplicative interaction = 0.09). There were similar synergistic associations between 25OHD and IL5, and several IFNα2 to Th2 cytokine ratios. This is the first study to provide evidence of interactions between vitamin D and the immune system in relation to breast cancer ER status, which may inform combinational use of vitamin D and anti-inflammatory drugs for cancer prevention and therapy.

  19. Effects of stress, mimicked by administration of corticosterone in drinking water, on the expression of chicken cytokine and chemokine genes in lymphocytes.

    Science.gov (United States)

    Shini, S; Kaiser, P

    2009-09-01

    In this study, we identify molecular mediators that participate in the regulation of the immune response during corticosterone-induced stress in chickens. At 7 weeks of age, 120 chickens were exposed for 1 week to corticosterone treatment. Cytokine and chemokine mRNA expression levels were evaluated in peripheral blood and splenic lymphocytes. Expression levels of interleukin (IL)-1beta, IL-6, IL-18 and transforming growth factor (TGF)-beta4 mRNA were significantly up-regulated in lymphocytes 3 h after first treatment with corticosterone. TGF-beta4 and IL-18 remained elevated 1 week post-initial treatment. Compared with controls, corticosterone-treated birds showed greater expression levels of chemokine (CC) mRNA, particularly for CCLi2, CCL5 (RANTES), CCL16 and CXCLi1, in peripheral and splenic lymphocytes 3 h post-initial exposure. CCLi2 mRNA was highly expressed in splenocytes at all time-points. Administration of corticosterone significantly increased circulating corticosterone concentrations and decreased total lymphocyte counts at 3, 24 h and 1 week post-initiation of corticosterone treatment. There was a positive correlation between plasma corticosterone concentrations and CCL5 and CCL16 mRNA at 3 h post-initial administration. At 1 week post-initial treatment, corticosterone concentrations correlated positively with CCL5 and negatively with IL-18 mRNA level. Conditions associated with significant changes in corticosterone levels might therefore affect the immune response by increasing pro-inflammatory responses, leading to potential modulation of the Th1/Th2 balance.

  20. Expressions and Significance of Th1/Th2/Th17 Cytokines and Antimyocardial Antibodies in Mouse Dilated ;Cardiomyopathy%Th1/Th2/Th17细胞因子及抗心肌抗体在小鼠扩张型心肌病中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    李丽萍; 孔清; 赖文盈; 潘晓芬; 伍伟锋

    2015-01-01

    Objective:To observe the expressions of Th1/Th2/Th1 7 cytokines and antimyocardial antibodies in mouse dilated cardiomyopathy (DCM),and explore their roles and significance in DCM pathogenesis.Methods:BALB/c mouse model of DCM was built with coxsackievirus(CVB3).Mice in control group were treated with phosphate-buffered saline (PBS)i.p. Mice were killed at the 24th week,and the fibrosis degree of myocardial tissue was observed by myocardial Masson’s staining. Expressions of Th1/Th2/Th1 7 cytokines in plasma were detected by using protein microarray.The mouse plasma levels of an-timyocardial antibodies such as adenine nucleotide translocator(ANT)antibody,β-myosin heavy chain(β-MHC)antibody,car-diac L-type calcium channel(CACH2),and anti-β1-adrenergic receptor(β1 AR)were measured by enzyme-linked immunosorbent assay (ELISA).Results:The result of myocardial pathological examination in DCM group fit the features of DCM 24 weeks af-ter virus infection.Compared with those in control group,expression levels of interleukin(IL)-2,IL-10,IL-13,IL-28 and TNF-αin DCM group decreased(P <0.05),however,the expression levels of IL-6,IL-1 7,IL-21 ,IL-22,IL-23 and TGF-βin-creased significantly(P <0.05).Meanwhile,compared with those in control group,the plasma levels of ANT andβ-MHC anti-bodies in DCM group increased significantly (P <0.05).Furthermore,positive correlation was found between level of IL-22 and level of anti-ANT according to correlative analysis(P <0.05 ).Conclusions:Immunologic derangement induced by imbal-ance of antimyocardial antibodies such as ANT and β-MHC,and Th1/Th2/Th1 7 cytokines such as IL-2、IL-10、IL-13、IL-28、TNF-α、IL-6、IL-1 7、IL-21 、IL-22、IL-23 and TGF-βmay play important roles in the pathogenesis of DCM.Furthermore,IL-22 may boost the production of ANT antibody.%目的::观察 Th1/Th2/Th17细胞因子及抗心肌抗体在小鼠扩张型心肌病(dilated cardiomyopathy,DCM)中的表达,并探讨其在 DCM 发病机制中

  1. Variable transcription of pro- and anti-inflammatory cytokines in phocine lymphocytes following canine distemper virus infection.

    Science.gov (United States)

    Seibel, H; Siebert, U; Rosenberger, T; Baumgärtner, W

    2014-10-15

    Canine distemper virus (CDV) is a highly contagious viral pathogen. Domesticated dogs are the main reservoir of CDV. Although phocine distemper virus was responsible for the recent epidemics in seals in the North and Baltic Seas, most devastating epidemics in seals were also caused by CDV. To further study the pathogenesis of CDV infection in seals, it was the aim of the present study to investigate the mechanisms of CDV induced immunosuppression in seals by analyzing the gene transcription of different pro- and anti-inflammatory cytokines in Concanavalin A (Con A) stimulated and non-stimulated phocine lymphocytes in vitro following infection with the CDV Onderstepoort (CDV-OND) strain. Phocine lymphocytes were isolated via density gradient centrifugation. The addition of 1 μg/ml Con A and virus was either performed simultaneously or lymphocytes were stimulated for 48 h with Con A prior to virus infection. Gene transcription of interleukin (IL)-6, IL-12 and tumor necrosis factor alpha (TNFα) as pro-inflammatory cytokines and IL-4, IL-10 and transforming growth factor beta (TGFβ) as anti-inflammatory cytokines were determined by using RT-qPCR. CDV-OND infection caused an initial increase of pro-inflammatory phocine cytokines mRNA 24h after infection, followed by a decrease in gene transcription after 48 h. A strong increase in the transcription of IL-4 and TGFβ was detected after 48 h when virus and mitogen were added simultaneously. An increased IL-10 production occurred only when stimulation and infection were performed simultaneously. Furthermore, an inhibition of IL-12 on IL-4 was noticed in phocine lymphocytes which were stimulated for 48 h prior to infection. In summary, the duration of the stimulation or the lymphocytes seem to have an important influence on the cytokine transcription and indicates that the outcome of CDV infection is dependent on various factors that might sensitize lymphocytes or make them more susceptible or reactive to CDV infection.

  2. Changes in the Th1 : Th2 Cytokine Bias in Pregnancy and the Effects of the Anti-Inflammatory Cyclopentenone Prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2

    Directory of Open Access Journals (Sweden)

    Lynne Sykes

    2012-01-01

    Full Text Available Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2 protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ12,14-Prostaglandin J2 (15dPGJ2 inhibits nuclear factor Kappa B (NF-κB in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ2 could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF-κB while simultaneously promoting Th2 interleukin 4 (IL-4 synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ2 or vehicle control and stimulated with phorbol myristyl acetate (PMA/ionomycin. The percentage of CD4+ cells producing interferon gamma (IFN-γ and tumor necrosis factor alpha (TNF-α in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ2 reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2+ve cells. 15dPGJ2 also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ2 suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.

  3. Recombinant ESAT-6-CFP10 Fusion Protein Induction of Th1/Th2 Cytokines and FoxP3 Expressing Treg Cells in Pulmonary TB.

    Directory of Open Access Journals (Sweden)

    Dolly Jackson-Sillah

    Full Text Available Early secretory antigenic target 6 (ESAT-6 and culture filtrate protein 10 (CFP-10 are Mycobacterium tuberculosis (Mtb-specific antigens that are secreted by actively metabolising bacteria and contribute to the virulence of the bacteria. Their ability to induce Treg and Th2 responses, particularly during the first two weeks of treatment, has not been comprehensively examined to date. The purpose of this work was to characterise Th1, Th2 and Treg responses to rESAT-6-CFP10 fusion protein in TB patients before and during the intensive phase of treatment and in healthy M.bovis BCG vaccinated donors.Forty-six newly diagnosed, HIV-negative, smear-positive pulmonary TB patients and 20 healthy donors were recruited in the UK and Ghana. Their peripheral blood mononuclear cells (PBMC were used in ex vivo ELISPOT and in vitro cultures to identify immunological parameters of interest.The study confirmed that protective immune responses to rESAT-6-CFP10 are impaired in active TB but improved during treatment: circulating antigen-specific IL-4-producing T-cells were increased in untreated TB but declined by two weeks of treatment while the circulating antigen-specific IFN-γ producing T cells which showed a transient rise at one week of treatment, persisted at baseline levels at two months of treatment. In vitro T cell proliferation and IFN-γ production were reduced, while IL-4 and CD4(+FoxP3(+CD25(hi cell expression were increased in response to rESAT-6-CFP10 fusion protein in untreated TB. These responses were reversed during early treatment of TB.These observations support further investigations into the possible utility of these parameters as markers of active disease and favourable treatment outcomes.

  4. Cytokine production of in vitro stimulated peripheral lymphocytes during the course of pregnancy and pseudopregnancy in the rat

    NARCIS (Netherlands)

    Faas, MM; Eenling, R; van der Schaaf, G; Moes, H; Heineman, MJ; Vos, P

    Problem Does maternal lymphocyte cytokine production after in vitro stimulation vary with the stage of pregnancy in the rat? Method of study Blood samples were taken during the estrus cycle in rats (n = 11). Thereafter, rats were rendered pregnant (n = 6) or pseudopregnant (n = 5) and blood samples

  5. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

    Science.gov (United States)

    Maj, Tomasz; Slawek, Anna

    2014-01-01

    Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs) derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA) were cocultured with CD4+ T cells derived from OT-II mice's (C57BL6/J-Tg(TcraTcrb)1100Mjb/J) spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU), activation of these cells (flow cytometry), cytokine profile (ELISA), and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear. PMID:24771983

  6. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

    Directory of Open Access Journals (Sweden)

    Tomasz Maj

    2014-01-01

    Full Text Available Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA were cocultured with CD4+ T cells derived from OT-II mice’s (C57BL6/J-Tg(TcraTcrb1100Mjb/J spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU, activation of these cells (flow cytometry, cytokine profile (ELISA, and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

  7. Serum cytokines, T lymphocyte subsets and STAT3 function in patients with herpes zoster as well as the intervention effect of mouse nerve growth factor

    Institute of Scientific and Technical Information of China (English)

    Yun Xu; Ling-Ling Tan; Kai Wang; Juan-Juan Zhang; Li-Jing Zhang

    2016-01-01

    Objective:To assess the levels of serum cytokines, T lymphocyte subsets and STAT3 in patients with herpes zoster as well as the intervention effect of mouse nerve growth factor. Methods:A total of 102 patients with herpes zoster were selected as observation group and received mouse nerve growth factor intervention, and 100 cases of normal people who received physical examination in our hospital during the same period as the healthy control group. The levels of serum Th1/Th2 cytokines, IgG subclass and complements and T lymphocyte subsets as well as STAT3 function of observation group before and after treatment and healthy control group were detected.Results: Serum IL-2 andγ-IFN levels of observation group after treatment were higher than those before treatment while IL-4, IL-5, IL-10 and TNF-α levels were lower than those before treatment (P<0.05); serum IgG1, IgG3, IgG4, C3 and C4 values of observation group after treatment were higher than those before treatment while IgG2 value was lower than that before treatment (P<0.05); CD3, CD4 and CD4/CD8 levels of observation group after treatment were higher than those before treatment while CD8 level was lower than that before treatment (P<0.05); STAT3, p-STAT3 and JAK2 expression levels of observation group after treatment were lower than those before treatment (P<0.05).Conclusions:There are abnormal immune system and STAT3 signaling pathway function in patients with herpes zoster, and mouse nerve growth factor intervention can restore multisystem balance and accelerate disease rehabilitation, and has positive clinical significance.

  8. Changes of fibrocytes and related Th1/Th2 cytokines in mice with radiation-induced pulmonary injury%纤维细胞和Th1/Th2型细胞因子在放射性肺损伤中的作用及相关机制

    Institute of Scientific and Technical Information of China (English)

    熊珊珊; 李若曦; 杜丽; 肖凤君; 徐龙; 刘坤璐; 杨陟华; 朱茂祥; 潘秀颉

    2013-01-01

    Objective To observe the changes of fibrocytes and Th1/Th2 cytokines in the lung of irradiated mice and explore its role in radiation-induced pulmonary injury.Methods The whole thorax of mice were irradiated with single 25 Gy of 60Co γ-rays in order to establish a model of pulmonary injury.The pathologic changes of lung were determined by Masson three-color stain and Hematoxylin and eosin stain.The concentration of collagen Ⅰ was assayed by microplate spectrophotometer.The number of fibrocytes in lung and the levels of MCP-1,MIP-1α and Th1/Th2 cytokines in BAL were measured with flow cytometry and liquid suspension array,respectively.Results Irradiated mice suffered with weight loss from 14 d to 3 month after irradiation (F =7.19,40.62,58.70,P <0.05).Pathological evidence demonstrated that the collagen fibers hyperplasia occurred at 1 month and aggravated at 3 month.Concentration of collagen Ⅰ (Z =-2.470,-2.236,P < 0.05) increased at 1 and 3 month post-irradiation.There were significant increase in the number of fibrocytes (Z =-2.19,-2.64,-2.64,P < 0.05) in pulmonary interstitium and the levels ofMCP-1 (Z=-2.35,-2.37,-2.34,P<0.05) andMIP-1α (Z=-2.43,-2.35,-2.35,P <0.05) in BAL from 14 d to 3 month.The levels of IFN-γ increased at 1 month (Z =-2.34P<0.05) and the expression of IL-12 decreased at3 and7 d (Z=-2.31,-2.30,P<0.05) while increased at 1 and 3 month (Z=-2.32,-2.12,P<0.05).IL-4 level were up from 7 d to 1 month (Z=-2.31,-2.35,-2.32,P<0.05),and IL-10 level went up on 3 d,at 1 month and 3 month post-irradiation (Z =-2.33,-2.37,-2.34,P < 0.05).Conclusions Fibrocytes are the important target of radiation-induced pulmonary injury.MCP-1and MIP-1α lead to fibrocytes recruitment and Th1/Th2 cytokines may be involved in this process.%目的 观察小鼠经60Co γ射线胸部照射后肺组织中纤维细胞和Th1/Th2型细胞因子变化规律,探究其在放射性肺损伤中的作用及相关机制.方法 小鼠经60Co

  9. Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status

    Directory of Open Access Journals (Sweden)

    Ana Claudia ARAUJO-PIRES

    2014-07-01

    Full Text Available Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas. Methods: The expression of TNF-α, IFN-γ, IL-17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array was accessed in active/progressive (N=40 versus inactive/stable (N=70 periapical granulomas (as determined by RANKL/OPG expression ratio, and also to compare these samples with a panel of control specimens (N=26. A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas. Results: The expression of all target cytokines was higher in the granulomas than in control samples. TNF-α, IFN-γ, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas, while in inactive lesions the expression levels of IL-4, IL-9, IL-10, IL-22 and FOXp3 were higher than in active granulomas. Five clusters were identified in inactive lesion groups, being the variance in the expression levels of IL-17, IL-10, FOXp3, IFN-γ, IL-9, IL-33 and IL-4 statistically significant (KW p<0.05. Three clusters were identified in active lesions, being the variance in the expression levels of IL-22, IL-10, IFN-γ, IL-17, IL-33, FOXp3, IL-21 and RANKL statistically significant (KW p<0.05. Conclusion: There is a clear dichotomy in the profile of cytokine expression in inactive and active periapical lesions. While the widespread cytokine expression seems to be a feature of chronic

  10. Molecular cloning of a Poria cocos protein that activates Th1 immune response and allays Th2 cytokine and IgE production in a murine atopic dermatitis model.

    Science.gov (United States)

    Lu, Ya-Ting; Kuan, Yen-Chou; Chang, Hui-Hsin; Sheu, Fuu

    2014-04-02

    Edible fungus Poria cocos (Schw.) Wolf is a cooking material that has myriad health benefits. However, its active constituents have not been well-defined. We previously purified an immunomodulatory protein, PCP, from P. cocos and described its biochemical features and its ability to activate primary macrophage via TLR4. In this study, we cloned the gene of PCP and demonstrated its ability to activate Th1 response in cell cultures and in mice. The complete cDNA sequence of PCP consisted of 807 bp, which included a 579 bp coding sequence that encoded 194 amino acids. With the addition of co-stimulatory CD3/CD28 signals, PCP significantly increased the surface expression of CD44 and CD69 on effector T cells. PCP could also up-regulate T-bet and STAT4 expressions and IFN-γ and IL-2 secretions. Oral administration of PCP suppressed the production of both total and OVA-specific IgG1 in serum and enhanced the amounts of serum and OVA-specific IgG2a and Th1-related cytokine production in BALB/c splenocytes. In addition, oral administration of PCP significantly reduced IL-4 and IgE expressions in a murine model of atopic dermatitis. In conclusion, these results provide evidence that PCP could regulate mammalian immune cells and reveal their pharmaceutical potential in developing therapeutic strategies against Th2-mediated immune disorders.

  11. "Comparative Study Of The Profiles Of Th1 And Th2 Cytokines In Patients With Sputum Smear- Positive Pulmonary Tuberculosis And PPD–Positive Healthy Persons And Their Changes During Treatment "

    Directory of Open Access Journals (Sweden)

    M. Hajiabdolbaghi

    2006-06-01

    Full Text Available Background and Aim: The better understanding of immunopathologic mechanism of tuberculosis (TB is necessary for the production of new vaccines and adjunctive immunomodulator drugs. Intended to this object, the following study including the measurement of serum concentrations of Th1 (Interferon (IFN-y and interkeukin (IL-2 and Th2 cytokines(IL-4AND IL-10 in patients with sputum smear-positive pulmonary TB and comparisons of them with PPpositive healthy persons, was designed. Materials and Methods: The HIV-negative patients that had sputum smear-positive pulmonary TB as defined WHO criteria and hospitalized in the infectious diseases ward of Imam Khomeini hospital or referred to health care centers in the south of Tehran, were included in the study. The PPD-positive healthy persons who were close contacts with pulmonary TB patients, were considered as control group. Results: In this research 34 active pulmonary TB patients (including17men and 17 womanand 23 healthy persons with PPD skin test results  or = 10mm (including 12men and 11 woman were studied. The mean ages of the patients and the healthy persons were 73 and 41 years and 74 and 27 years, respectively. The mean serum IFN-Y concentration was significantly higher in TB patients but the mean serum IL-2 IL-4and IL-10 concentrations were significantly higher in healthy persons. The com parison of the mean serum levels of these cytokines before and during treatment (about 2 months after starting treatment showed that the amounts of IFN-y and IL4 were increased and the amounts of IL2 and IL-10 were decreased but only the changes of IL-10 were statistically significant. There were no effect on the cytokine changes before and during treatment by age and gender of the patients. Conclusion: The results of the study of serum Th1 and Th2 cytokines in pulmonary TB patients were different in comparison with the results of the studies of peripheral blood mononuclear cells (PBMCs stimulated with

  12. Chromone linked nitrone derivative induces the expression of iNOS2 and Th1 cytokines but reduces the Th2 response in experimental visceral leishmaniasis.

    Science.gov (United States)

    Mallick, Suvadip; Halder, Subhadra; Dutta, Aritri; Dey, Somaditya; Paul, Kausik; Maiti, Sourav; Bandyopadhyay, Chandrakanta; Saha, Bhaskar; Pal, Chiranjib

    2013-04-01

    In our previous work we have shown that the novel synthetic chromone derivative could effectively inhibit the Leishmania donovani replication in vitro and in vivo with less cytotoxicity on murine splenocytes. The aim of the present study is to explore the possible mechanism of anti-leishmanial effect of C-(6-methyl-4-oxo-4H-1-benzopyran-3-yl)-N-(p-tolyl) nitrone (designated as NP1) in vitro and in vivo in experimental visceral leishmaniasis caused by L. donovani. The cytotoxic effect of this derivative was studied in murine peritoneal macrophages by MTT method. NP1 at a dose of 17.06 μM showed 50% inhibition on L. donovani promastigotes but found less cytotoxic to the RAW 264.7 cells. Even the higher concentration of IC50 (up to four fold) did not exert much cytotoxic effect on RAW 264.7. Interestingly, NP1 at lower concentration (8.53 μM) could inhibit 50% of intracellular amastigotes in murine peritoneal macrophages. L. donovani is known to exert its pathogenic effects mainly by the suppression of NO generation and subversion of the cellular inflammatory responses in the macrophages. NP1 was found to induce a potent host-protective immune response by enhancing NO generation and iNOS2 expression at mRNA level and by up-regulating proinflammatory cytokines such as IL-12 and IFN-γ and limiting the expression of IL-10 in vivo. The NO dependent killing was further confirmed in iNOS(-/-) mice compared to wild type. In agreement with the fact, induced synthesis of IL-12 and IFN-γ and associated down-regulation of IL-10 by the treatment of NP1 clearly indicated the possibility of novel strategy of drug development against Leishmania infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Change of Th1/Th2 Cytokine Equilibrium in Rats with Severe Sepsis and Therapeutic Effect of Recombinant Interleukin-12 and Shenmai Injection(参麦注射液)

    Institute of Scientific and Technical Information of China (English)

    YU Yong-hao; CUI Nai-qiang; FU Qiang; LI Jun

    2005-01-01

    Objective: To evaluate the dynamic change of Th1/Th2 cytokines in serum, peritoneal lavage fluid (PLF) and splenic macrophages (SM) in rats with severe peritonitis, and to observe the therapeutic preparation. Methods: Severe peritonitis (SP) model was induced by intraperitoneal injection of E. coli and B. frag, and mild peritonitis (MP) model was induced by cecal ligation and punching. Then the following experiments were done: (1) Survival rates of animals after every 6 hrs in the 72 hrs after modeling were recorded, serum and PLF levels of cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ),and interleukin-10 (IL-10), 6 hrs, 12 hrs, 24 hrs and 48 hrs after modeling were measured. (2) Model rats were treated with rlL-12 or SMI, the survival rate was recorded and serum levels of TNF-α, INF-γ, and IL-10before and after treatment were measured, and (3) amount of these cytokines produced by SM were determined 6 hrs, 12 hrs and 24 hrs after treatment. The survival rates and levels of cytokines were then compared between the groups (model group treated with rlL-12 or SMI, untreated model group, and blank group). Results: Serum and PLF levels of IFN-γ, TNF-α at all the time points in SP rats were significantly lower than those in MP rats while those of IL-10 6 hrs and 12 hrs after modeling were significantly higher in the former than that in the latter ( P<0.05). IFN-γ secretion of SM in SP rats was significantly higher than that in MP rats 6 hrs after modeling (P<0.05). Administration of rlL-12 or SMI given before modeling could improve the survival rate of the model rats (P<0.05) and cause significant increase of the serum level and SM secretion of IFN-γ. Conclusion: Imbalance in promoting/antagonizing inflammatory cytokines and Th2 response dominance appear in SP rats early at the initiating stage, and SM secretion of inflammation promoting factor also reduces. Administration in time of rlL-12 and SMI, may increase the survival

  14. Levels of Th1 and Th2 cytokines in elderly patients with eczema%老年湿疹患者T辅助细胞相关细胞因子水平分析

    Institute of Scientific and Technical Information of China (English)

    杨敏; 郝洪军; 张春媚; 常建民; 李邻峰

    2012-01-01

    目的 研究老年湿疹患者Th1/Th2细胞因子的血清水平与湿疹的发展及其临床表现的相关性. 方法 应用酶联免疫吸附法(ELISA)测定50例老年湿疹患者(≥60岁)白介素(IL)-2、4、10、12和肿瘤坏死因子(TNF-α)的血清水平并与34例健康老年人(对照组)进行比较;比较急性和慢性,或泛发性和局限性湿疹上述细胞因子的水平差异. 结果 老年湿疹组IL-2 [(16.03±0.47)比(15.72±0.33) μg/L]、IL-4 [(14.04±0.56)比(13.56±0.16)μg/L]、IL-10[(33.01±5.40)比(29.49±1.07) μg/L]、IL-12 [(39.32±3.54)比(37.93±1.17) μg/L]和TNF-α [(27.33±0.72)比(26.38±0.48) μg/L]水平均高于对照组(t/t'=3.55,5.74,4.4 9,2.58,6.69,均P<0.05).急性湿疹组血清细胞因子水平均高于对照组(t/t'=3.59,6.44,4.68,3.35,2.00,均P<0.05);慢性湿疹组中IL-2、IL-4、IL-10和TNF-α的血清水平高于对照组(t'=2.46,5.50,3.83,3.10,均P<0.05),而IL-12水平与对照组的差异无统计学意义(t'=1.77,P>0.05);急性与慢性湿疹患者血清细胞因子的水平差异无统计学意义(P>0.05).泛发性与局限性湿疹患者血清IL-2、II4、IL-10和IL-12、TNF-α的水平差异无统计学意义(t=0.18,5.74,4.49,0.91,0.25,1.11,均P>0.05). 结论细胞因子IL-2、IL-4、IL-10、Th1/Th2和TNF-α可能与老年人湿疹发生相关,不同临床类型的老年湿疹患者可能并无特定的Th1/Th2细胞因子变化模式.%Objective To investigate the serum levels of Th1 and Th2 cytokines and explore its roles in development and clinical features in the elderly patients with eczema. Methods The serum levels of interleukin-2(IL-2),interleukin 4(IL-4),interleukin-10(IL-10),interleukin-12(IL-12) and tumor necrosis factor alpha (TNF-α) were derected in 50 elderly patients with eczema and 34 healthy elderly as control by enzyme-linked immunosorbent assay (ELISA). The above cytokines were compared between acute and chronic,generalized and localized eczema. Results The serum

  15. Fulminant lymphocytic choriomeningitis virus-induced inflammation of the CNS involves a cytokine-chemokine-cytokine-chemokine cascade

    DEFF Research Database (Denmark)

    Christensen, Jeanette E; Simonsen, Stine; Fenger, Christina

    2009-01-01

    Intracerebral inoculation of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) normally results in fatal CD8+ T cell mediated meningoencephalitis. However, in CXCL10-deficient mice, the virus-induced CD8+ T cell accumulation in the neural parenchyma is impaired, and only 30...

  16. The changes of T lymphocytes and cytokines in ICR mice fed with Fe3O4 magnetic nanoparticles

    Directory of Open Access Journals (Sweden)

    Wang J

    2011-04-01

    Full Text Available Jun Wang1, Baoan Chen1, Nan Jin1, Guohua Xia2, Yue Chen1, Ying Zhou1, Xiaohui Cai1,2, Jiahua Ding1, Xiaomao Li3, Xuemei Wang41Department of Hematology, Zhongda Hospital, 2Department of Medical Laboratory, Medical School, Southeast University, Nanjing, People's Republic of China; 3Department of Physics, University of Saarland, Saarbruecken, Germany; 4National Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory, Southeast University, Nanjing, People’s Republic of ChinaAbstract: The aim of this article is to study the changes inhibited T lymphocytes and cytokines related to the cellular immunity in ICR (imprinting control region mice fed with Fe3O4 magnetic nanoparticles (Fe3O4-MNPs. The Fe3O4-MNPs were synthesized, and their characteristics such as particle size, zeta potential, and X-ray diffraction patterns were measured and determined. All ICR mice were sacrificed after being exposed to 0, 300, 600, and 1200 mg/kg of Fe3O4-MNPs by single gastric administration for 14 days. Splenocytes proliferation was indicated with stimulate index by MTT assay; release of cytokines in the serum of ICR mice was detected by enzyme-linked immunosorbent assay, and the phenotypic analyses of T-lymphocyte subsets were performed using flow cytometry. Our results indicated that there were no significant differences in splenocyte proliferation and release of cytokines between exposed and control groups. Furthermore, there was no significant difference in the proportions of T-lymphocyte subsets in the low-dose Fe3O4-MNPs group when compared to the control group, but the proportions of CD3+CD4+ and CD3+CD8+ T-lymphocyte subsets both in the medium- and high-dose Fe3O4-MNPs groups were higher than those in the control group. It is concluded that a high dose of Fe3O4-MNPs, to some extent, could influence in vivo immune function of normal ICR mice.Keywords: Fe3O4, magnetic nanoparticles, splenocyte proliferation, release of cytokines, T-lymphocyte subsets, ICR

  17. The impact of maternal HIV infection on cord blood lymphocyte subsets and cytokine profile in exposed non-infected newborns

    Directory of Open Access Journals (Sweden)

    Reis-Alves Suiellen C

    2011-02-01

    Full Text Available Abstract Background Children born to HIV+ mothers are exposed intra-utero to several drugs and cytokines that can modify the developing immune system, and influence the newborn's immune response to infections and vaccines. We analyzed the relation between the distribution of cord blood lymphocyte subsets and cytokine profile in term newborns of HIV+ mothers using HAART during pregnancy and compared them to normal newborns. Methods In a prospective, controlled study, 36 mother-child pairs from HIV+ mothers and 15 HIV-uninfected mothers were studied. Hematological features and cytokine profiles of mothers at 35 weeks of pregnancy were examined. Maternal and cord lymphocyte subsets as well as B-cell maturation in cord blood were analyzed by flow cytometry. The non-stimulated, as well as BCG- and PHA-stimulated production of IL2, IL4, IL7, IL10, IL12, IFN-γ and TNF-alpha in mononuclear cell cultures from mothers and infants were quantified using ELISA. Results After one year follow-up none of the exposed infants became seropositive for HIV. An increase in B lymphocytes, especially the CD19/CD5+ ones, was observed in cord blood of HIV-exposed newborns. Children of HIV+ hard drug using mothers had also an increase of immature B-cells. Cord blood mononuclear cells of HIV-exposed newborns produced less IL-4 and IL-7 and more IL-10 and IFN-γ in culture than those of uninfected mothers. Cytokine values in supernatants were similar in infants and their mothers except for IFN-γ and TNF-alpha that were higher in HIV+ mothers, especially in drug abusing ones. Cord blood CD19/CD5+ lymphocytes showed a positive correlation with cord IL-7 and IL-10. A higher maternal age and smoking was associated with a decrease of cord blood CD4+ cells. Conclusions in uninfected infants born to HIV+ women, several immunological abnormalities were found, related to the residual maternal immune changes induced by the HIV infection and those associated with antiretroviral

  18. TLR2 and TLR4 signaling pathways are required for recombinant Brucella abortus BCSP31-induced cytokine production, functional upregulation of mouse macrophages, and the Th1 immune response in vivo and in vitro.

    Science.gov (United States)

    Li, Jia-Yun; Liu, Yuan; Gao, Xiao-Xue; Gao, Xiang; Cai, Hong

    2014-09-01

    Brucella abortus is a zoonotic Gram-negative pathogen that causes brucelosis in ruminants and humans. Toll-like receptors (TLRs) recognize Brucella abortus and initiate antigen-presenting cell activities that affect both innate and adaptive immunity. In this study, we focused on recombinant Brucella cell-surface protein 31 (rBCSP31) to determine its effects on mouse macrophages. Our results demonstrated that rBCSP31 induced TNF-α, IL-6 and IL-12p40 production, which depended on the activation of mitogen-activated protein kinases (MAPKs) by stimulating the rapid phosphorylation of p38 and JNK and the activation of transcription factor NF-κB in macrophages. In addition, continuous exposure (>24 h) of RAW264.7 cells to rBCSP31 significantly enhanced IFN-γ-induced expression of MHC-II and the ability to present rBCSP31 peptide to CD4(+) T cells. Furthermore, we found that rBCSP31 could interact with both TLR2 and TLR4. The rBCSP31-induced cytokine production by macrophages from TLR2(-/-) and TLR4(-/-) mice was lower than that from C57BL/6 macrophages, and the activation of NF-κB and MAPKs was attenuated in macrophages from TLR2(-/-) and TLR4(-/-) mice. In addition, CD4(+) T cells from C57BL/6 mice immunized with rBCSP31 produced higher levels of IFN-γ and IL-2 compared with CD4(+) T cells from TLR2(-/-) and TLR4(-/-) mice. Macrophages from immunized C57BL/6 mice produced higher levels of IL-12p40 than those from TLR2(-/-) and TLR4(-/-) mice. Furthermore, immunization with rBCSP31 provided better protection in C57BL/6 mice than in TLR2(-/-) and TLR4(-/-) mice after B. abortus 2308 challenge. These results indicate that rBCSP31 is a TLR2 and TLR4 agonist that induces cytokine production, upregulates macrophage function and induces the Th1 immune response.

  19. Gamma c-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Kasprzycka, Monika; Zhang, Qian; Witkiewicz, Agnieszka

    2008-01-01

    In this study, we demonstrate that malignant mature CD4(+) T lymphocytes derived from cutaneous T cell lymphomas (CTCL) variably display some aspects of the T regulatory phenotype. Whereas seven cell lines representing a spectrum of primary cutaneous T cell lymphoproliferative disorders expressed...... that the T regulatory cell features are induced in CTCL T cells by common gamma chain signaling cytokines such as IL-2 and do not represent a fully predetermined, constitutive phenotype independent of the local environmental stimuli to which these malignant mature CD4(+) T cells become exposed....

  20. Fulminant lymphocytic choriomeningitis virus-induced inflammation of the CNS involves a cytokine-chemokine-cytokine-chemokine cascade

    DEFF Research Database (Denmark)

    Christensen, Jeanette E; Simonsen, Stine; Fenger, Christina

    2009-01-01

    Intracerebral inoculation of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) normally results in fatal CD8+ T cell mediated meningoencephalitis. However, in CXCL10-deficient mice, the virus-induced CD8+ T cell accumulation in the neural parenchyma is impaired, and only 30...... the expression of CXCL10 in the CNS of LCMV-infected mice. Using mice deficient in type I IFN receptor, type II IFN receptor, or type II IFN, as well as bone marrow chimeras expressing CXCL10 only in resident cells or only in bone marrow-derived cells, we analyzed the up-stream regulation as well as the cellular...... source of CXCL10. We found that expression of CXCL10 initially depends on signaling through the type I IFN receptor, while late expression and up-regulation requires type II IFN produced by the recruited CD8+ T cells. Throughout the infection, the producers of CXCL10 are exclusively resident cells...

  1. Role of Proinflammatory Cytokines in Thermal Activation of Lymphocyte Recruitment in Breast Tumor Microvessels

    Science.gov (United States)

    2005-03-01

    interactionsI IL-6 trans-signaling mechanism J__ MEK/ERK Inside-out signaling Cancer Immunology , Immunotherapy (in press) DYNAMIC CONTROL OF LYMPHOCYTE...venules, tumor microvessels, fever Cancer Immunology , Immunotherapy (in press) ABSTRACT Migration of blood-borne lymphocytes into tissues involves a...the basis for novel approaches to improve recruitment of immune effector cells to tumor sites. 2 Cancer Immunology , Immunotherapy (in press) High

  2. 免疫增强治疗对隐性梅毒患者Th1/Th2细胞因子的影响分析%Analysis of the effect of immune enhancement therapy on the Th1/Th2 cytokines of patients with latent syphilis

    Institute of Scientific and Technical Information of China (English)

    黄显翔

    2014-01-01

    目的:对隐性梅毒患者进行免疫增强治疗,并观察其对患者Th1/Th2细胞因子的影响。方法:收治隐性梅毒患者40例,通过对比分析法对其临床资料进行分析,并应用免疫增强疗法进行治疗。用随机抽取法将患者分为对照组与治疗组,对照组采用苄星青霉素常规治疗法进行治疗,治疗组应用苄星青霉素常规治疗法联合金菌灵胶囊进行治疗,每组20例,并选取20例普通患者作为正常组进行对比性分析,应用酶联免疫吸附试验对这3组血清中的IFN-γ、IL-2、IL-10、IL-4的水平进行检测并分析。结果:相较于对照组正常人而言,隐性梅毒患者血清中的IFN-γ、IL-2的水平明显要低,而IL-10、IL-4的水平明显要高,其数据对比差异有统计学意义,P<0.01。治疗组治疗3个月以及6个月后其血清中IFN-γ、IL-2水平呈现升高趋势,而IL-10、IL-4的水平呈现下降趋势。结论:隐性梅毒患者在接受免疫增强治疗过程中有利于调节其紊乱的免疫调节功能,改变Th2型细胞因子占据主导地位的局势,从而增强患者机体免疫力,提高治疗效果。%Objective:To observe the effect of Th1/Th2 cytokines of patients with latent syphilis that were treated with immune enhancement therapy.Methods:40 patients with latent syphilis were selected.Their data were clinical analyzed through comparative analysis,and all patients were treated with immune enhancement therapy.They were divided into the control group and the treatment group.The control group was treated with benzyl penicillin of conventional therapy.The treatment group was treated with benzyl penicillin of conventional therapy combined with golden carbendazim capsule.There were 20 cases in each group.20 normal patients were selected as the normal group for comparative analysis.The levels of serum 1FN-γ,1L-2,1L-10, 1L-4 of these 3 groups were detected and analyzed by enzyme

  3. 初发1型糖尿病儿童辅助性Th1细胞因子紊乱相关因素分析%Factors associated with Th1 cytokine disorders in children with newly diagnosed type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    吕玲; 刘佳悦; 马静; 林书祥; 黄乐

    2013-01-01

    细胞等各临床指标水平.结果 病例组细胞因子IL-12水平高于对照组(P<0.001).病例组IL-18水平与发病时间呈负相关(r=-0.413,P=0.015);中性粒细胞与IL-1β水平呈正相关(r=0.413,P=0.023);外周血WBC与IL-18水平亦呈正相关(r=0.352,P=0.038).WBC增高组细胞因子IL-1β、IL-12、IL-18水平高于WBC正常组(均P<0.05).结论 1型糖尿病患儿存在Th1细胞分泌细胞因子紊乱,感染可进一步提高细胞因子的分泌水平,可能推动了早期糖尿病起病过程.

  4. Effects of leptin on airway inflammation and the expression of Th1/Th2 cytokines in asthmatic rats%瘦素对支气管哮喘大鼠气道炎症及Th1/Th2细胞因子表达作用的影响

    Institute of Scientific and Technical Information of China (English)

    曹娟; 陈建辉; 朱述阳

    2009-01-01

    Objective To investigate the effects of hptin on airway inflammation and the expression of Th1/Th2 cytokines. Methods The obesity and acute asthma models were established in 40 female SD rats, which were randomly divided into a normal weight control group (group A), a normal weight asthmatic group (group B), a normal weight intervention group (group C), an obese control group (group D) and an obese asthmatic group (group E). The airway resistance and airway responsiveness were calculated by transpulmonary pressure and gas flow rate. The numbers of leukocytes, eosinophils (EOS) and neutrephils (N) in brenchoalveolar lavage fluid (BALF) were counted. The concentrations of interleukin-4 (IL-4), interferon-γ(IFN-γ) and leptin in serum and BALF were determined by ELISA. The protein and Mrna expression of leptin was measured by Western blot and RT-PCR respectively. Results The airway resistance in group C and E [(0.890±0.106)cm H2O·ml-1·s-1 (1.024±0.096)cm H2O·ml-1·s-1(1.129±0.107) cm H2O·ml-1·s-1, (0.946±0.104) cm H2O·ml-1·s-1, (1.124±0.095)cm H2O·ml-1·s-1, (1.135±0.105) cm H2O·ml-1·s-1,respectively.] was increased significantly compared to group B [(0.638±0.128) cm H2O·ml-1·s-1, (0.745±0.073) cm H2O·ml-1·s-1,(0.773±0.090) cm H2O·ml-1·s-1] (q=7.128, 8.712, 8.318, 11.300, 11.258, 11.447, all P<0.05). The numbers of leukocyte and neutrophils in group C and E [(91±9)×104/ml, (108±21)×104/ml, (12.4±4.0)×104/ml, (14.2±5.9)×104/ml, respectively.] were increased significantly compared to group B [(79±7)×104/ml, (2.4±1.1)×104/ml] (q= 2.923, 7.063, 8.629, 10.182,all P<0.05). The concentrations of IFN-γ were [(42.3±3.5) ng/L, (45.1±4.8) ng/L, (19.2±1.8) ng/L, (20.3±1.5)ng/L] in group C and E respectively, which were significantly higher than those of group B[(16.5±1.4) ng/L,(9.3±1.0) ng/L] (q= 21.607, 23.952, 16.919, 18.799, all P<0.05). The protein and Mrna expression of leptin in lung tissue in group C and E[(0.40±0.07)ng/L,(0

  5. The crude latex of Euphorbia tirucalli modulates the cytokine response of leukocytes, especially CD4+ T lymphocytes

    Directory of Open Access Journals (Sweden)

    Bethânia A. Avelar

    2011-08-01

    Full Text Available The plants of the Euphorbiaceae family, especially those of the genus Euphorbia, are frequently used by Brazilian folk communities to treat a wide variety of infectious, tumoral and inflammatory illnesses. Among the species of this genus, Euphorbia tirucalli L. is widely used in some Brazilian regions, such as the Jequitinhonha River Valley. There is evidence that the latex produced by E. tirucalli has antiviral and antitumor activities, but little is known about the mechanisms involved in these effects. It is likely that the mechanism for such activities involves leukocyte activation and cytokine production. In this work, we aimed to evaluate the production of type 1 (TNF-α and IFN-γ and type 2 (IL-4 and IL-10 cytokines by circulating leukocyte subsets submitted to brief stimulation with the crude latex of E. tirucalli. Peripheral blood leukocytes of twenty healthy subjects were submitted to 4 h incubation with crude E. tirucalli latex diluted in dimethylsulfoxide. After the incubation period, the cells were stained with FITC-conjugated monoclonal antibodies specific to the cell surface receptors CD4, CD8 and CD14, and to PE-conjugated monoclonal antibodies specific to the cytokines TNF-α, IFN-γ, IL-4 and IL-10. The acquisition and analysis of data were performed by flow cytometry. The results showed a significant increase (p<0.05 in the percentage of CD4+ T lymphocytes positive for the type 1 cytokines TNF-α and IFN-γ. Neutrophils and CD8+ T lymphocytes showed a mixed profile of cytokine production, characterized by an increase in the percentage of cells expressing IFN-γ, TNF-α, and IL-10. The data indicate a predominant type 1 cytokine response. The findings presented suggest that the effect popularly attributed to E. tirucalli usage may be attributed to its effect on the production of TNF-α and IFN-γ. However, the relationship between the in vitro and in vivo effects of E. tirucalli needs to be investigated.

  6. Exercise Training, Lymphocyte Subsets and Their Cytokines Production: Experience of an Italian Professional Football Team and Their Impact on Allergy

    Science.gov (United States)

    2014-01-01

    Background. In recent years, numerous articles have attempted to shed light on our understanding of the pathophysiological mechanisms of exercise-induced immunologic changes and their impact on allergy and asthma. It is known that lymphocyte subclasses, cytokines, and chemokines show modifications after exercise, but outcomes can be affected by the type of exercise as well as by its intensity and duration. Interesting data have been presented in many recent studies on mouse models, but few studies on humans have been performed to check the long-term effects of exercise over a whole championship season. Methods. This study evaluated lymphocyte subsets and their intracellular IL-2, IL-4, TNF-α, and IFN-γ production in professional football (soccer) players, at three stages of the season, to evaluate if alterations occur, particularly in relation to their allergic status. Results and Conclusion. Despite significant mid-season alterations, no significant lymphocyte subclasses count modifications, except for NKs that were significantly higher, were observed at the end. IL-2 and IL-4 producing cells showed a significant decrease (P = 0.018 and P = 0.001, but in a steady fashion for IL-4), confirming the murine data about the potential beneficial effects of aerobic exercise for allergic asthma. PMID:25050349

  7. Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study

    Science.gov (United States)

    Wu, Wei; Zheng, Ya-li; Tian, Li-ping; Lai, Jian-bo; Hu, Chan-chan; Zhang, Peng; Chen, Jing-kai; Hu, Jian-bo; Huang, Man-li; Wei, Ning; Xu, Wei-juan; Zhou, Wei-hua; Lu, Shao-jia; Lu, Jing; Qi, Hong-li; Wang, Dan-dan; Zhou, Xiao-yi; Duan, Jin-feng; Xu, Yi; Hu, Shao-hua

    2017-01-01

    This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders. PMID:28074937

  8. Exercise Training, Lymphocyte Subsets and Their Cytokines Production: Experience of an Italian Professional Football Team and Their Impact on Allergy

    Directory of Open Access Journals (Sweden)

    Stefano R. Del Giacco

    2014-01-01

    Full Text Available Background. In recent years, numerous articles have attempted to shed light on our understanding of the pathophysiological mechanisms of exercise-induced immunologic changes and their impact on allergy and asthma. It is known that lymphocyte subclasses, cytokines, and chemokines show modifications after exercise, but outcomes can be affected by the type of exercise as well as by its intensity and duration. Interesting data have been presented in many recent studies on mouse models, but few studies on humans have been performed to check the long-term effects of exercise over a whole championship season. Methods. This study evaluated lymphocyte subsets and their intracellular IL-2, IL-4, TNF-α, and IFN-γ production in professional football (soccer players, at three stages of the season, to evaluate if alterations occur, particularly in relation to their allergic status. Results and Conclusion. Despite significant mid-season alterations, no significant lymphocyte subclasses count modifications, except for NKs that were significantly higher, were observed at the end. IL-2 and IL-4 producing cells showed a significant decrease (P=0.018 and P=0.001, but in a steady fashion for IL-4, confirming the murine data about the potential beneficial effects of aerobic exercise for allergic asthma.

  9. T lymphocytes in the lesional skin and the levels of peripheral blood cytokines in patients with psoriasis

    Directory of Open Access Journals (Sweden)

    İbrahim Kökçam

    2011-03-01

    Full Text Available In the current study, it was aimed to investigate the roles of tissue cellular immunity and serum levels of cytokines in the patients with plaque psoriasis treated with calcipotriol-betamethasone dipropionate.Materials and methods: The study included 20 patients with psoriasis. Peripheral blood and biopsy samples were collected from lesional and normal skins before and after treatment. The results were compared with each other.Results: Immunohistochemical examination revealed significant elevations of CD4+, CD8+ and CD25+ T lymphocytes in the lesional tissues when compared to that in the healthy tissues and post treatment tissue (p0.05. The levels of IL–4, IL–10, TNF-α, IFN-γ and TGF-β1 in serum were not significantly different between before and after treatment periods (p>0.05.Conclusion: Our study demonstrated that there were infiltration of CD4+ and CD8+ cell in the lesional skin and CD8+ T-lymphocytes were the dominant cell types. The improvement of the lesions and significant decreases in CD4+ and CD8+ T-cells in accordance with the treatment strongly support the hypothesis that Th lymphocytes may have prominent roles in the immunopathogenesis of the disease. However, our findings showed that sufficient T-cells still remains in the tissue, which is consistent with the chronic characteristic of the disease, and the topical treatment could not be able to prevent the activation of the disease.

  10. Treatment With Lenalidomide Modulates T-Cell Immunophenotype and Cytokine Production in Patients With Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Lee, Bang-Ning; Gao, Hui; Cohen, Evan N.; Badoux, Xavier; Wierda, William G.; Estrov, Zeev; Faderl, Stefan H.; Keating, Michael J.; Ferrajoli, Alessandra; Reuben, James M.

    2015-01-01

    BACKGROUND Lenalidomide, an immunomodulatory agent, has activity in lymphoproliferative disorders. The authors, therefore, evaluated its effects on T-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia (CLL). METHODS To study the immunomodulatory effects of lenalidomide in CLL, the authors recruited 24 patients with untreated CLL enrolled in a phase 2 clinical trial of lenalidomide and obtained peripheral blood specimens for immunologic studies consisting of enumeration of T cells and assessing their ability to synthesize cytokines after activation through T-cell receptor (TCR). RESULTS After 3 cycles of therapy, patients had a significant reduction in percentage (%) and absolute lymphocyte count (ALC) and an increase in percentage of T cells, percentage of activated CD8+ T cells producing IFN-γ, and percentage of regulatory T (TR) cells when compared with their respective levels before treatment. After 15 cycles of treatment, responder patients had significant reduction in percentage of lymphocytes and ALC, percentage of activated CD4+ T cells producing IL-2, IFN-γ, or TNF-α, and percentage of TR cells when compared with their perspective levels after 3 cycles of treatment. Furthermore, the numbers of activated CD4+ T cells producing IL-2, IFN-γ, or TNF-α, activated CD8+ T cells producing IFN-γ, and TR cells normalized to the range of healthy subjects. CONCLUSIONS Treatment with lenalidomide resulted in the normalization of functional T-cell subsets in responders, suggesting that lenalidomide may modulate cell-mediated immunity in patients with CLL. PMID:21858802

  11. Alteration in lymphocyte responses, cytokine and chemokine profiles in chickens infected with genotype VII and VIII velogenic Newcastle disease virus.

    Science.gov (United States)

    Rasoli, Mehdi; Yeap, Swee Keong; Tan, Sheau Wei; Moeini, Hassan; Ideris, Aini; Bejo, Mohd Hair; Alitheen, Noorjahan Banu Mohamed; Kaiser, Pete; Omar, Abdul Rahman

    2014-01-01

    Newcastle disease (ND) is a highly contagious avian disease and one of the major causes of economic losses in the poultry industry. The emergence of virulent NDV genotypes and repeated outbreaks of NDV in vaccinated chickens have raised the need for fundamental studies on the virus-host interactions. In this study, the profiles of B and T lymphocytes and macrophages and differential expression of 26 immune-related genes in the spleen of specific-pathogen-free (SPF) chickens, infected with either the velogenic genotype VII NDV strain IBS002 or the genotype VIII NDV strain AF2240, were evaluated. A significant reduction in T lymphocyte population and an increase in the infiltration of IgM+ B cells and KUL01+ macrophages were detected in the infected spleens at 1, 3 and 4 days post-infection (dpi) (P<0.05). The gene expression profiles showed an up-regulation of CCLi3, CXCLi1, CXCLi2 (IL-8), IFN-γ, IL-12α, IL-18, IL-1β, IL-6, iNOS, TLR7, MHCI, IL-17F and TNFSF13B (P<0.05). However, these two genotypes showed different cytokine expression patterns and viral load. IBS002 showed higher viral load than AF2240 in spleen at 3 and 4dpi and caused a more rapid up-regulation of CXCLi2, IFN-γ, IL-12α, IL-18, IL-1β, iNOS and IL-10 at 3dpi. Meanwhile, the expression levels of CCLI3, CXCLi1, IFN-γ, IL-12α, IL-1β and iNOS genes were significantly higher in AF2240 at 4dpi. In addition, the expression levels of IL-10 were significantly higher in the IBS002-infected chickens at 3 and 4dpi. Hence, infection with velogenic genotype VII and VIII NDV induced different viral load and production of cytokines and chemokines associated with inflammatory reactions.

  12. ESA刺激华支睾吸虫感染小鼠脾细胞分泌Th1/Th2的动态观察%Th1/Th2 cytokine profile in spleen mononuclear cells of mice infected with Clonorchis stimulated by excretory-secretory antigen

    Institute of Scientific and Technical Information of China (English)

    郭倩倩; 戴其锋; 付琳琳; 汤仁仙; 夏惠; 郑葵阳; 刘宜升; 杜文平; 曹磊磊; 赵昆

    2009-01-01

    目的 观察华支睾吸虫分泌排泄抗原(ESA)刺激感染小鼠脾脏单个核细胞Th1/Th2细胞因子的动态变化.方法 双抗体夹心ELISA法检测华支睾吸虫感染后不同时间小鼠脾细胞培养上清中IFN-γ,IL-4的动态变化.结果 自感染后1w起IFN-γ的表达量开始上升,第4w达高峰(P<0.05),此后开始下降,至第12w水平接近正常.与IFN-γ不同,IL-4的表达自感染后第1w起持续升高,直至观察结束的12w(P<0.05). 结论 初步结果提示华支睾吸虫感染后急性期转向慢性期的过程中Th1/Th2细胞因子的表达经历了由Th1优势应答向Th2优势应答的转变.

  13. Dual effects of vitamin D-induced alteration of TH1/TH2 cytokine expression: enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease

    DEFF Research Database (Denmark)

    Matheu, Victor; Bäck, Ove; Mondoc, Emma

    2003-01-01

    BACKGROUND: Vitamin D, a common food additive, has been shown to prevent the induction of experimental autoimmune diseases in mice. A possible immune deviation from T(H)1 to T(H)2 responses has been postulated. Although there is no doubt about the beneficial effects of vitamin D, its role in alle...... hold promising beneficial effects in airway eosinophilia....

  14. Up-regulation of T lymphocyte and antibody production by inflammatory cytokines released by macrophage exposure to multi-walled carbon nanotubes.

    Science.gov (United States)

    Grecco, Ana Carolina P; Paula, Rosemeire F O; Mizutani, Erica; Sartorelli, Juliana C; Milani, Ana M; Longhini, Ana Leda F; Oliveira, Elaine C; Pradella, Fernando; Silva, Vania D R; Moraes, Adriel S; Peterlevitz, Alfredo C; Farias, Alessandro S; Ceragioli, Helder J; Santos, Leonilda M B; Baranauskas, Vitor

    2011-07-01

    Our data demonstrate that multi-walled carbon nanotubes (MWCNTs) are internalized by macrophages, subsequently activating them to produce interleukin (IL)-12 (IL-12). This cytokine induced the proliferative response of T lymphocytes to a nonspecific mitogen and to ovalbumin (OVA). This increase in the proliferative response was accompanied by an increase in the expression of pro-inflammatory cytokines, such as interferon-gamma (IFNγ), tumor necrosis factor-alpha (TNFα) and IL-6, in mice inoculated with MWCNTs, whether or not they had been immunized with OVA. A decrease in the expression of transforming growth factor-beta (TGFβ) was observed in the mice treated with MWCNTs, whereas the suppression of the expression of both TGFβ and IL-10 was observed in mice that had been both treated and immunized. The activation of the T lymphocyte response by the pro-inflammatory cytokines leads to an increase in antibody production to OVA, suggesting the important immunostimulatory effect of carbon nanotubes.

  15. Up-regulation of T lymphocyte and antibody production by inflammatory cytokines released by macrophage exposure to multi-walled carbon nanotubes

    Science.gov (United States)

    Grecco, Ana Carolina P.; Paula, Rosemeire F. O.; Mizutani, Erica; Sartorelli, Juliana C.; Milani, Ana M.; Longhini, Ana Leda F.; Oliveira, Elaine C.; Pradella, Fernando; Silva, Vania D. R.; Moraes, Adriel S.; Peterlevitz, Alfredo C.; Farias, Alessandro S.; Ceragioli, Helder J.; Santos, Leonilda M. B.; Baranauskas, Vitor

    2011-07-01

    Our data demonstrate that multi-walled carbon nanotubes (MWCNTs) are internalized by macrophages, subsequently activating them to produce interleukin (IL)-12 (IL-12). This cytokine induced the proliferative response of T lymphocytes to a nonspecific mitogen and to ovalbumin (OVA). This increase in the proliferative response was accompanied by an increase in the expression of pro-inflammatory cytokines, such as interferon-gamma (IFNγ), tumor necrosis factor-alpha (TNFα) and IL-6, in mice inoculated with MWCNTs, whether or not they had been immunized with OVA. A decrease in the expression of transforming growth factor-beta (TGFβ) was observed in the mice treated with MWCNTs, whereas the suppression of the expression of both TGFβ and IL-10 was observed in mice that had been both treated and immunized. The activation of the T lymphocyte response by the pro-inflammatory cytokines leads to an increase in antibody production to OVA, suggesting the important immunostimulatory effect of carbon nanotubes.

  16. Regulation of nasal airway homeostasis and inflammation in mice by SHP-1 and Th2/Th1 signaling pathways.

    Directory of Open Access Journals (Sweden)

    Seok Hyun Cho

    Full Text Available Allergic rhinitis is a chronic inflammatory disease orchestrated by Th2 lymphocytes. Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1 is known to be a negative regulator in the IL-4α/STAT-6 signaling pathway of the lung. However, the role of SHP-1 enzyme and its functional relationship with Th2 and Th1 cytokines are not known in the nasal airway. In this study, we aimed to study the nasal inflammation as a result of SHP-1 deficiency in viable motheaten (mev mice and to investigate the molecular mechanisms involved. Cytology, histology, and expression of cytokines and chemokines were analyzed to define the nature of the nasal inflammation. Targeted gene depletion of Th1 (IFN-γ and Th2 (IL-4 and IL-13 cytokines was used to identify the critical pathways involved. Matrix metalloproteinases (MMPs were studied to demonstrate the clearance mechanism of recruited inflammatory cells into the nasal airway. We showed here that mev mice had a spontaneous allergic rhinitis-like inflammation with eosinophilia, mucus metaplasia, up-regulation of Th2 cytokines (IL-4 and IL-13, chemokines (eotaxin, and MMPs. All of these inflammatory mediators were clearly counter-regulated by Th2 and Th1 cytokines. Deletion of IFN-γ gene induced a strong Th2-skewed inflammation with transepithelial migration of the inflammatory cells. These findings suggest that SHP-1 enzyme and Th2/Th1 paradigm may play a critical role in the maintenance of nasal immune homeostasis and in the regulation of allergic rhinitis.

  17. Alteration of neurotrophin and cytokine expression in lymphocytes as novel peripheral markers of spatial memory deficits induced by prenatal stress.

    Science.gov (United States)

    Pascuan, C G; Di Rosso, M E; Pivoz-Avedikian, J E; Wald, M R; Zorrilla Zubilete, M A; Genaro, A M

    2017-05-01

    Much evidence has suggested that early life adversity can have a lasting effect on behavior. The aim of this study was to explore the impact of prenatal exposure to stress on cognition in adult life and how it impacts chronic stress situations. In addition, we investigated the participation of glucocorticoids, neurotrophins and cytokines in prenatal stress effects. For this purpose, pregnant mice were placed in a cylindrical restraint tube for 2h daily during the last week of pregnancy. Control pregnant females were left undisturbed during their entire pregnancy period. Object-in-place task results showed that adult female mice exposed to prenatal stress exhibited an impairment in spatial memory. However, in the alternation test this memory deficit was only found in prenatally stressed mice submitted to chronic stress. This alteration occurred in parallel with a decrease in BDNF, an increase in glucocorticoid receptors and an alteration of Th1/Th2 in the hippocampus. Interestingly, these changes were observed in peripheral lymph nodes as well. However, none of the mentioned changes were observed in adult male mice. These results indicate that lymphoid cells could be good candidates as peripheral markers of susceptibility to behavioral alterations associated with prenatal exposure to stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. 蛤蚧对S180荷瘤小鼠Th1/Th2免疫细胞平衡的影响%Influence of Gejie on the balance of Th1/Th2 Cytokines in Mice Bearing S180 Tumor Cells

    Institute of Scientific and Technical Information of China (English)

    周蓓; 陈豪; 吴丽丽; 吴燕春

    2016-01-01

    目的:观察蛤蚧(GJ)对S180荷瘤小鼠Th1/Th2细胞因子的影响.方法:采用S180瘤株皮下接种昆明种小鼠造荷瘤模型.设正常组、模型组、环磷酰胺组(CTX),GJ高、中、低剂量组.给药14天后,计算抑瘤率、免疫器官指数;酶联免疫吸附法检测Th1类细胞因子(IL-2、IFN-γ)、Th2类细胞因子(IL-4、IL-10)的表达及计算Th1/Th2比值.结果:①与模型组比较,GJ低剂量组肿瘤生长明显受到抑制(P<0.05);②与CTX比较,GJ低剂量组脾脏指数明显升高(P<0.05),GJ中、高剂量组胸腺指数明显升高(P<0.05);③与模型组比较,GJ低剂量组IFN-γ、IL-2含量升高(P<0.05),低、中剂量组IL-4含量明显降低(P<0.05),GJ各剂量组IL-10含量降低,差异无统计学意义(P>0.05);④GJ低剂量组IFN-γ/IL-4比值、IL-2/IL-4比值均高于模型组(P<0.05).结论:GJ可有效纠正荷瘤小鼠Th1/Th2失衡,增强机体的抗肿瘤免疫功能.

  19. 化疗对乳腺癌患者外周血Th1和Th2类细胞因子基因表达的影响%Impact of Chemotherapy on Peripheral Th1 and Th2 Cytokines Gene Expression in Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    刘海荣; 李岩; 赵跃然; 许晓群

    2008-01-01

    [目的]探讨化疗对乳腺癌患者Th1和Th2类细胞因子的基因表达的影响.[方法]采用逆转录聚合酶链反应(RT-PCR)技术,检测乳腺癌患者化疗前后外周血单个核细胞(PBMC)Th1和Th2类细胞因子mRNA表达水平的变化.[结果]乳腺癌组IL-2mRNA(4)、IL-12mRNA(5)阳性表达均较正常对照组(10,14)及良性乳腺肿瘤组(11,16)明显减少(P<0.05);IL-6mRNA(19)、IL-10mRNA(16)较正常对照组及良性乳腺肿瘤组(8,5)显著增加(P<0.05);正常对照组及良性乳腺肿瘤组Th1和Th2类细胞因子mRNA表达无显著性差异(P>0.05).乳腺癌化疗3个周期后.IL-6mRNA(8/36)和IL-10mRNA(6/38)阳性表达均较化疗前(19/25.16/28)显著降低(P<0.05);IL-2mRNA(14/30)和IL-12mRNA(15/29)阳性表达均较化疗前(4/40,5/39)显著升高(P<0.05).[结论]化疗可使早期乳腺癌患者Th2类细胞因子的强势表达向Th1类逆转,改善患者的免疫状况.

  20. Perforin-deficient CD8+ T cells mediate fatal lymphocytic choriomeningitis despite impaired cytokine production

    DEFF Research Database (Denmark)

    Storm, Pernille; Bartholdy, Christina; Sørensen, Maria Rathmann

    2006-01-01

    invariably succumb to i.c. infection with LCMV strain Armstrong, although a few days later than matched wild-type mice. Upon further investigation, we found that this delay correlates with the delayed recruitment of inflammatory cells to the central nervous system (CNS). However, CD8(+) effector T cells were......Intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (LCMV) is one of the most studied models for virus-induced immunopathology, and based on results from perforin-deficient mice, it is currently assumed that fatal disease directly reflects perforin-mediated cell lysis. However......, recent studies have revealed additional functional defects within the effector T cells of LCMV-infected perforin-deficient mice, raising the possibility that perforin may not be directly involved in mediating lethal disease. For this reason, we decided to reevaluate the role of perforin in determining...

  1. Influence of in vivo hypobaric hypoxia on function of lymphocytes, neutrocytes, natural killer cells, and cytokines

    DEFF Research Database (Denmark)

    Klokker, M; Kharazmi, A; Galbo, H

    1993-01-01

    of an increased concentration of lymphocytes. The absolute and relative concentration of CD16+ natural killer (NK) cells increased markedly during hypoxia and returned to pretest values after 2 h of recovery. The NK cell activity of blood mononuclear cells (BMNC, %lysis/fixed no. of BMNC) boosted with interferon......-alpha, interleukin-2 (IL-2), and indomethacin rose in parallel with unboosted NK cell activity during hypoxia. The percentage of CD4+ and CD8+ cells declined during hypoxia, whereas the absolute concentration of both CD8+ cells and CD14+ monocytes increased. Although the BMNC composition varied, the proliferative....... The chemiluminescence response of neutrocytes increased 2 h after hypoxia. It was concluded that acute hypoxia induced marked alterations in the immune system and that the NK cells are especially sensitive to the hypoxic stimulus....

  2. Is inflammatory bowel disease in dogs and cats associated with a Th1 or Th2 polarization?

    Science.gov (United States)

    Heilmann, Romy M; Suchodolski, Jan S

    2015-12-15

    Mucosal immunity involves complex interactions to generate either immune tolerance or active immune responses. An imbalance of pro- and anti-inflammatory cytokines and chemokines that drive the recruitment of immune cells to the intestinal mucosa are a key characteristic of inflammatory bowel disease in humans, where distinctive helper-T-lymphocyte profiles help to discriminate between Crohn's disease and ulcerative colitis. This review evaluates the current veterinary literature to determine whether a Th1/Th2 (and possibly also Th17) polarization also exists in canine and feline inflammatory bowel disease.

  3. Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC patients

    Directory of Open Access Journals (Sweden)

    Bouzouita Kamel

    2004-09-01

    Full Text Available Abstract Background Undifferentiated Nasopharyngeal Carcinoma (NPC patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL and tumor- infiltrating (TIL lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10 and three immunoglobulin isotypes (IgM, IgG, IgA. Methods Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA. Data were analysed using Student's t-test and probability values below 5% were considered significant. Results The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002, IL-10 (p = 0,020, IgM (p= 0,0003 and IgG (p Conclusion Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC.

  4. Sickle cell anemia induces changes in peripheral lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in patients under treatment.

    Science.gov (United States)

    Castilhos, Lívia G; Doleski, Pedro H; Bertoldo, Tatiana M D; Passos, Daniela F; Bertoncheli, Claudia de M; Rezer, João F P; Schlemmer, Josiane B; Leal, Daniela B R

    2015-07-01

    Sickle cell anemia (SCA) is characterized by hemoglobin polymerization that results in sickle-shaped red blood cells. The vascular obstruction by sickle erythrocytes is often inflammatory, and purinergic system ecto-enzymes play an important role in modulating the inflammatory and immune response. This study aimed to evaluate the E-NTPDase and E-ADA activities in lymphocytes of SCA treated patients, as well as verify the cytokine profile in this population. Fifteen SCA treated patients and 30 health subjects (control group) were selected. The peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated from clot formation for the cytokines quantification. E-NTPDase (ATP and ADP as substrate) and E-ADA (adenosine as substrate) activities were increased in lymphocytes from SCA patients (P<0.001). The TNF-α and IL-6 serum cytokines showed decreased on SCA patients comparing to control (P<0.001). The regulation of extracellular nucleotides released in response to hypoxia and inflammation through E-NTPDase and E-ADA enzymes represent an important control of purine-mediated in the SCA disease, avoiding elevated adenosine levels in the extracellular medium and consequent organ injuries in these patients. The pro-inflammatory cytokines decreased levels by use of hydroxyurea occur in attempt to reduce the pro-inflammatory response and prevent vaso-oclusive crisis.

  5. Cytokine Contents in Chronic Lymphocytic Leukemia: Association with ZAP70 Expression

    Directory of Open Access Journals (Sweden)

    Nilgün Işıksaçan

    2016-08-01

    Full Text Available Objective: Chronic lymphocytic leukemia (CLL is a disease that shows varying clinical progression, and expression of the protein tyrosine kinase ZAP70 has been described as a very valuable prognostic factor. Patients with ZAP70 positivity are characterized by worse clinical course and significantly shorter progression-free and overall survival. In this study, intracytoplasmic interferon gamma (IFN-γ and interleukin-4 (IL-4 content of T, B, and CLL cells in CLL patients and their correlations with Rai staging and ZAP70 positivity were investigated. Materials and Methods: CLL patients newly diagnosed or in followup at the İstanbul University İstanbul Medical Faculty Hematology Department were included in this study. These patients were classified according to Rai staging and ZAP70 expression. IL-4, IFN-γ, and ZAP70 expressions in peripheral blood T, B, and CLL cells were measured by four-color flow cytometry. Results: There was a statistically significant correlation between advanced disease and ZAP70 positivity. IL-4-secreting T cells were significantly increased; however, IFN-γ secretion was significantly decreased in CLL patients compared to healthy individuals, whereas IL-4-secreting B cells were significantly diminished in contrast to T cells. Conclusion: These findings suggest damage in the cellular immunity and that IL-4 might lead to many complications and may be important in disease progression.

  6. Acellular pertussis booster in adolescents induces Th1 and memory CD8+ T cell immune response.

    Directory of Open Access Journals (Sweden)

    Nikolaus Rieber

    Full Text Available In a number of countries, whole cell pertussis vaccines (wcP were replaced by acellular vaccines (aP due to an improved reactogenicity profile. Pertussis immunization leads to specific antibody production with the help of CD4(+ T cells. In earlier studies in infants and young children, wcP vaccines selectively induced a Th1 dominated immune response, whereas aP vaccines led to a Th2 biased response. To obtain data on Th1 or Th2 dominance of the immune response in adolescents receiving an aP booster immunization after a wcP or aP primary immunization, we analyzed the concentration of Th1 (IL-2, TNF-α, INF-γ and Th2 (IL-4, IL-5, IL-10 cytokines in supernatants of lymphocyte cultures specifically stimulated with pertussis antigens. We also investigated the presence of cytotoxic T cell responses against the facultative intracellular bacterium Bordetella pertussis by quantifying pertussis-specific CD8(+ T cell activation following the aP booster immunization. Here we show that the adolescent aP booster vaccination predominantly leads to a Th1 immune response based on IFNgamma secretion upon stimulation with pertussis antigen, irrespective of a prior whole cell or acellular primary vaccination. The vaccination also induces an increase in peripheral CD8(+CD69(+ activated pertussis-specific memory T cells four weeks after vaccination. The Th1 bias of this immune response could play a role for the decreased local reactogenicity of this adolescent aP booster immunization when compared to the preceding childhood acellular pertussis booster. Pertussis-specific CD8(+ memory T cells may contribute to protection against clinical pertussis.

  7. Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Friedline, Randall H; Ko, Hwi Jin; Jung, Dae Young; Lee, Yongjin; Bortell, Rita; Dagdeviren, Sezin; Patel, Payal R; Hu, Xiaodi; Inashima, Kunikazu; Kearns, Caitlyn; Tsitsilianos, Nicholas; Shafiq, Umber; Shultz, Leonard D; Lee, Ki Won; Greiner, Dale L; Kim, Jason K

    2016-03-01

    Obesity is characterized by a dysregulated immune system, which may causally associate with insulin resistance and type 2 diabetes. Despite widespread use of nonobese diabetic (NOD) mice, NOD with severe combined immunodeficiency (scid) mutation (SCID) mice, and SCID bearing a null mutation in the IL-2 common γ chain receptor (NSG) mice as animal models of human diseases including type 1 diabetes, the underlying metabolic effects of a genetically altered immune system are poorly understood. For this, we performed a comprehensive metabolic characterization of these mice fed chow or after 6 wk of a high-fat diet. We found that NOD mice had ∼50% less fat mass and were 2-fold more insulin sensitive, as measured by hyperinsulinemic-euglycemic clamp, than C57BL/6 wild-type mice. SCID mice were also more insulin sensitive with increased muscle glucose metabolism and resistant to diet-induced obesity due to increased energy expenditure (∼10%) and physical activity (∼40%) as measured by metabolic cages. NSG mice were completely protected from diet-induced obesity and insulin resistance with significant increases in glucose metabolism in peripheral organs. Our findings demonstrate an important role of genetic background, lymphocytes, and cytokine signaling in diet-induced obesity and insulin resistance. © FASEB.

  8. 谷氨酰胺双肽对造血干细胞移植后患者血清Th1/Th2类细胞因子水平的影响%Effects of Glutamine Supplementation on Th1/Th2 Cytokines Level in Patients Undergoing Hematopoietic Stem Cell Transplantation

    Institute of Scientific and Technical Information of China (English)

    周红升; 胡金梅; 张东华; 黄伟; 肖毅; 李登举; 孟凡凯; 刘文励

    2006-01-01

    目的 研究谷氨酰胺双肽对造血干细胞移植患者血清Th1/Th2细胞因子水平的影响,及对移植后急性移植物抗宿主病(GVHD)的预防作用.方法 将20例接受异基因造血干细胞移植患者随机分为两组,谷氨酰胺组10例,对照组10例.从移植后当天至第20天,谷氨酰胺组患者除接受标准胃肠外营养支持外,每天给予N(2)-L-丙氨酰-L-谷氨酰胺200ml;对照组采用不含谷氨酰胺的标准化胃肠外营养支持.两组均采用改良白消安加环磷酰胺(BuCy2)预处理方案,采用环孢霉素加霉酚酸酯预防移植物抗宿主病(GVHD),分别于预处理当天, 移植后第7、14、21、28和42天收集患者血清标本,采用酶联免疫吸附实验(ELISA)分别检测肿瘤坏死因子α(TNF-α)、干扰素γ(INF-γ)、白介素2(IL-2)、 IL-4、 IL-10的水平,同时监测两组GVHD发生率及严重程度.结果 谷氨酰胺组TNF-α、INF-γ和IL-2水平较对照组低,其中TNF-α、INF-γ与对照组差异有显著意义(P<0.05);谷氨酰胺组IL-4和IL-10水平略高于对照组,但仅移植后第42天差异有显著意义(P<0.05).GVHD发生两组无明显差异.结论 谷氨酰胺能使造血干细胞移植患者的Th1/Th2细胞因子向有利于预防GVHD的方向偏移.

  9. Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Bendtzen, Klaus; Beck-Nielsen, H

    1997-01-01

    Interleukin (IL)-1 is a potent inducer of bone resorption, and an increased secretion of the IL-1 agonists IL-1 alpha and IL-1 beta relative to the IL-1 receptor antagonist (IL-1ra) has been proposed as a mechanism leading to post-menopausal osteoporosis. T-lymphocytes are capable of secreting bone...... resorptive cytokines and have also been linked with bone metabolism and the development of osteoporosis. Cytokine secretion from whole blood cell cultures was compared between two randomized groups of healthy early post-menopausal women (mean age 52.5 yrs, N = 91) and lymphocyte subsets were quantitated...... by flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups...

  10. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Miroslawa Pietruczuk; Milena I Dabrowska; Urszula Wereszczynska-Siemiatkowska; Andrzej Dabrowski

    2006-01-01

    AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP).METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5,10 and 30 by means of flow cytometry.RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of Tover B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28,CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5,IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells.CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.

  11. Cytotoxic effector functions of T cells are not required for protective immunity against fatal Rickettsia typhi infection in a murine model of infection: Role of TH1 and TH17 cytokines in protection and pathology.

    Directory of Open Access Journals (Sweden)

    Kristin Moderzynski

    2017-02-01

    Full Text Available Endemic typhus caused by Rickettsia (R. typhi is an emerging febrile disease that can be fatal due to multiple organ pathology. Here we analyzed the requirements for protection against R. typhi by T cells in the CB17 SCID model of infection. BALB/c wild-type mice generate CD4+ TH1 and cytotoxic CD8+ T cells both of which are sporadically reactivated in persistent infection. Either adoptively transferred CD8+ or CD4+ T cells protected R. typhi-infected CB17 SCID mice from death and provided long-term control. CD8+ T cells lacking either IFNγ or Perforin were still protective, demonstrating that the cytotoxic function of CD8+ T cells is not essential for protection. Immune wild-type CD4+ T cells produced high amounts of IFNγ, induced the release of nitric oxide in R. typhi-infected macrophages and inhibited bacterial growth in vitro via IFNγ and TNFα. However, adoptive transfer of CD4+IFNγ-/- T cells still protected 30-90% of R. typhi-infected CB17 SCID mice. These cells acquired a TH17 phenotype, producing high amounts of IL-17A and IL-22 in addition to TNFα, and inhibited bacterial growth in vitro. Surprisingly, the neutralization of either TNFα or IL-17A in CD4+IFNγ-/- T cell recipient mice did not alter bacterial elimination by these cells in vivo, led to faster recovery and enhanced survival compared to isotype-treated animals. Thus, collectively these data show that although CD4+ TH1 cells are clearly efficient in protection against R. typhi, CD4+ TH17 cells are similarly protective if the harmful effects of combined production of TNFα and IL-17A can be inhibited.

  12. Effect of Glucocorticoid on Disbalance of Th1/Th2 Cytokines in Asthmatic Patients%糖皮质激素对哮喘患者Th1/Th2类细胞因子水平失衡的影响

    Institute of Scientific and Technical Information of China (English)

    张晓宇; 钟立厚

    2004-01-01

    目的为了解糖皮质激素对哮喘患者Th1/Th2类细胞因子水平失衡的影响,探讨吸入糖皮质激素治疗哮喘的机制.方法取外周血,用ELISA法检测患者治疗前后和对照组血浆IL-4(白介素-4)、IL-12(白介素-12)、IgE的水平,并对统计结果进行统计分析.结果哮喘组治疗后较治疗前血浆IL-4、IgE和PEF(峰值呼气流速)变异率均下降(P<0.05 );IL-12的浓度升高(P<0.05).哮喘组治疗前血浆IL-4、IgE和PEF变异率均高于对照组(P<0.01);IL-12的浓度低于对照组(P<0.01).经布地奈得(BUD)治疗后,IL-4和IgE浓度仍高于对照组(P<0.01,P<0.05);IL-12低于对照组(P<0.05);PFE变异率与对照组相比无显著性差异.经相关分析:IL-4同IgE和 PEF变异率呈正相关(r=0.64,r=0.52;P<0.05,P<0.05);IL-12同IgE和PEF变异率呈负相关(r=-0.61,r=-0.49;P<0.05,P<0.05 );IL-4 同IL-12呈负相关(r=-0.86,P<0.01).结论糖皮质激素治疗哮喘的机制可能是抑制TH2类细胞因子的过度分泌,调节TH亚群功能失衡.

  13. 流式细胞术检测慢性淋巴细胞性甲状腺炎患者外周血Th1、Th2细胞的意义%Significance of the T helper 1 and T helper 2 lymphocytes in peripheral blood of patients with chronic lymphocytic thyroiditis as detected by flow cytometry

    Institute of Scientific and Technical Information of China (English)

    王云云; 宋进展; 吴汉妮; 钱伟

    2009-01-01

    检测慢性淋巴细胞甲状腺炎(CLT)患者外周血Th1、Th2细胞的水平,探讨Th1细胞占CD4~+T细胞比例(Th1%)、Th2细胞占CD4~+T细胞比例(Th2%)、Th1/Th2在各组间的差异和意义及分别与血清中针对甲状腺特异抗体的相关性.收集45例CLT患者外周血,分为甲状腺功能正常组15例和甲状腺功能减退组30例,20例健康人外周血作为对照组;采用胞内细胞因子染色流式细胞术检测Th1%和Th2%;应用电化学发光法检测甲状腺自身抗体--甲状腺球蛋白抗体(TgAb)和甲状腺过氧化物酶抗体(TPOAb)水平.结果显示,两组CLT患者外周血Th1%、Th1/Th2均高于正常对照组,差异均有统计学意义(P0. 05) , and the difference in Th2% showed no significant change (P>0. 05). There were significant correlations between the positive expression of serum thyroid autoanti-body(TPOAb, TgAb) and Th1% as well as the Th1/Th2 ratio. It is concluded that the increase of Th1% and the imbalance of Th1/Th2 may play an important role in the occurrence and process of CLT, and that the detection of Th1/Th2 cells by flow cytometry can be recognized as a reliable way to study the immune state of autoimmune thyroiditis.

  14. Circulating sCD138 and Some Angiogenesis-Involved Cytokines Help to Anticipate the Disease Progression of Early-Stage B-Cell Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Syndecan-1 (CD138 is a transmembrane heparin sulfate proteoglycan expressed on distinct stages of differentiation of B-lymphoid cells. Its prognostic value in B-cell chronic lymphocytic leukemia (B-CLL has not been evaluated so far. The serum concentration of sCD138 and some angiogenesis-involved cytokines: vascular endothelial growth factor (VEGF, basis fibroblast growth factor (bFGF, and endostatin were studied in 52 previously untreated patients with B-CLL. We found that bFGF and sCD138 levels were significantly higher in B-CLL patients than in controls. In patients with sCD138 level or endostatin level below the median value the lymphocyte count was higher than in patients with serum level of those cytokines above the median value. In patients with progressive disease bFGF level was significantly higher and sCD138 level significantly lower than in patients with stable one. Moreover, high sCD138 level was associated with longer lymphocyte doubling-free survival, and, on the limit of statistical significance, a high endostatin level was associated with shorter progression-free survival. We conclude that serum sCD138 level is increased in early stage B-CLL patients and may have a positive prognostic value as to the dynamics of the disease.

  15. Up-regulation of T lymphocyte and antibody production by inflammatory cytokines released by macrophage exposure to multi-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Grecco, Ana Carolina P; Mizutani, Erica; Peterlevitz, Alfredo C; Ceragioli, Helder J; Baranauskas, Vitor [Faculdade de Engenharia Eletrica e Computacao, Universidade de Campinas, Campinas, SP (Brazil); Paula, Rosemeire F O; Sartorelli, Juliana C; Milani, Ana M; Longhini, Ana Leda F; Oliveira, Elaine C; Pradella, Fernando; Silva, Vania D R; Moraes, Adriel S; Farias, Alessandro S; Santos, Leonilda M B, E-mail: leonilda@unicamp.br [Laboratorio de Neuroimunologia, Departamento Genetica, Evolucao e Bioagentes, Instituto de Biologia, Universidade de Campinas, Campinas, SP (Brazil)

    2011-07-01

    Our data demonstrate that multi-walled carbon nanotubes (MWCNTs) are internalized by macrophages, subsequently activating them to produce interleukin (IL)-12 (IL-12). This cytokine induced the proliferative response of T lymphocytes to a nonspecific mitogen and to ovalbumin (OVA). This increase in the proliferative response was accompanied by an increase in the expression of pro-inflammatory cytokines, such as interferon-gamma (IFN{gamma}), tumor necrosis factor-alpha (TNF{alpha}) and IL-6, in mice inoculated with MWCNTs, whether or not they had been immunized with OVA. A decrease in the expression of transforming growth factor-beta (TGF{beta}) was observed in the mice treated with MWCNTs, whereas the suppression of the expression of both TGF{beta} and IL-10 was observed in mice that had been both treated and immunized. The activation of the T lymphocyte response by the pro-inflammatory cytokines leads to an increase in antibody production to OVA, suggesting the important immunostimulatory effect of carbon nanotubes.

  16. Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis.

    Science.gov (United States)

    Wang, Zhigang; Chen, Zhe; Chen, Tao; Yi, Tao; Zheng, Zhou; Fan, Hong; Chen, Zebin

    2017-02-01

    Berberine, one of the active alkaloids from Rhizoma Coptidis, has been indicated to have anti-inflammatory and immunosuppressive properties. The aim of this study was to determine the role of berberine on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its potential mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cells infiltration, anti-OVA IgG levels, IgE concentration in serum, and the tetramer(+)CD8(+) cells. In homogenized footpad tissue, the production of Th1-mediated cytokines including IFN-γ, TNF-α, and IL-2 were suppressed following the administration of berberine. Detailed studies revealed that berberine prevented differentiation into Th1 cells in the OVA-primed lymphocytes, resulting from suppressing the expression of T-bet and secretion of IFN-γ but not IL-4. Concanavalin A stimulation assay and MTT assay also indicated inhibiting effect of berberine treatment on IFN-γ production and decreased cytotoxicity in lymphocytes proliferation, respectively. Additionally, berberine obviously decreased the cell apoptosis and enzymatic activity of caspase-3, which was further confirmed by the facts that berberine clearly lowered Bax/Bcl-2 ratio and expression of cleaved caspase-3 protein. On correlation analysis, the percentage of apoptotic cells showed a significant positive relationship with IFN-γ/IL-4 ratio of supernatant from footpad tissue in berberine-treated DTH mice. These results demonstrated that berberine attenuated Th1-mediated inflammation in OVA-induced DTH by curbing Th1 response and inhibiting cell apoptosis, suggesting a therapeutic potential for berberine for the treatment of type IV hypersensitivity.

  17. Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice.

    Science.gov (United States)

    Li, Jinyu; Wei, Yi; Li, Xue; Zhu, Dashuai; Nie, Bo; Zhou, Jingwei; Lou, Lixia; Dong, Bin; Wu, Aiming; Che, Yongzhe; Chen, Meng; Zhu, Lingqun; Mu, Mingwei; Chai, Limin

    2017-01-05

    Xian-Fang-Huo-Ming-Yin (XFHM), a traditional herbal formula, has been used to treat sores and carbuncles for hundreds of years in Asia. Nowadays, its clinical effects in treatment of rheumatoid arthritis (RA) have been validated. In this study, we want to study its possible molecular mechanisms of regulating the differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis (CIA) mice for RA treatment. A high performance liquid chromatography-electrospray ionization/mass spectrometer (HPLC-ESI/MS(n)) system was used to analyze the constituents of XFHM granules. An arthritics mouse model was induced by collagen and leflunomide (LEF) was used as a positive control medicine. Pathological changes at the metatarsophalangeal joint were studied through Safranin O and immunohistochemical staining. The differentiation of T, B and NK cells was examined by flow cytometry and pro-inflammatory cytokines were assayed using an Inflammation Antibody Array assay. The expression of key molecules of the nuclear factor κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways in spleen were studied by western-blot analysis. In our study. 21 different dominant chemical constituents were identified in XFHM. Treatment with XFHM suppressed the pathological changes in arthrosis of CIA. Additionally, XFHM down-regulated the proliferation and differentiation of CD3(+) T cells and CD3(-)CD19(+) B cells significantly. However, XFHM had no significant effect on CD3(-)NK1.1(+) NK cells. Further study showed that the production of pro-inflammatory cytokines had been suppressed by inhibiting the activation of NF-κB and JAK/STAT signaling. XFHM can regulate and maintain the immunologic balance of lymphocytic immunity and inhibit the production of pro-inflammatory cytokines, thus suppressing the pathological changes of RA. Therefore, XFHM may be used as an application of traditional medicine against RA

  18. Identification of Immunodominant Th1-type T cell Epitopes from Schistosoma japonicum 28 kDa Glutathione-S-transferase, a Vaccine Candidate

    Institute of Scientific and Technical Information of China (English)

    Guang-Fu LI; Guan-Ling WU; Yong WANG; Zhao-Song ZHANG; Xin-Jun WANG; Min-Jun JI; Xiang ZHU; Feng LIU; Xiao-Ping CAI; Hai-Wei WU

    2005-01-01

    Th1-type cytokines produced by the stimulation of Th1-type epitopes derived from defined schistosome-associated antigens are correlated with the development of resistance to the parasite infection.Schistosoma mansoni 28 kDa glutathione-S-transferase (Sm28GST), a major detoxification enzyme, has been recognized as a vaccine candidate and a phase Ⅱ clinical trial has been carried out. Sheep immunized with recombinant Schistosoma japonicum 28GST (Sj28GST) have shown immune protection against the parasite infection. In the present study, six candidate peptides (P1, P2, P3, P4, P7 and P8) from Sj28GST were predicted, using software, to be T cell epitopes, and peptides P5 and P6 were designed by extending five amino acids at the N-terminal and C-terminal of P1, respectively. The peptide 190-211 aa in Sj28GST corresponding to the Th1-type epitope (190-211 aa) identified from Sm28GST was selected and named P9.The nine candidate peptides were synthesized or produced as the fusion protein with thioredoxin in the pET32c(+)/BL21(DE3) system. Their capacity to induce a Th1-type response in vitro was measured using lymphocyte proliferation, cytokine detection experiments and flow cytometry. The results showed that P6(73-86 aa) generated the strongest stimulation effect on T cells among the nine candidate peptides, and drove the highest level of IFN-γ and IL-2. Therefore, P6 is a functional Th1-type T cell epitope that is different from that in Sm28GST, and will be useful for the development of effective vaccines which can trigger acquired immunity against S. japonicum. Moreover, our strategy of identifying the Th1-type epitope by a combination of software prediction and experimental confirmation provides a convenient and cost-saving alternative approach to previous methods.

  19. Intestinal Irradiation and Fibrosis in a Th1-Deficient Environment

    Energy Technology Data Exchange (ETDEWEB)

    Linard, Christine, E-mail: christine.linard@irsn.fr [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France); Billiard, Fabienne; Benderitter, Marc [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France)

    2012-09-01

    Purpose: Changes in the Th1/Th2 immune balance may play a role in increasing the incidence of radiation-induced toxicity. This study evaluates the consequences of Th1 deficiency on intestinal response (fibrosis and T cell trafficking) to abdominal irradiation and examines in mucosa and mesenteric lymph nodes (MLN) the differential involvement of the two Th1 pathways, T-bet/STAT1 and IL-12/STAT4, in controlling this balance in mice. Methods and Materials: Using T-bet-deficient mice (T-bet{sup -/-}), we evaluated the mRNA and protein expression of the Th1 pathways (IFN-{gamma}, T-bet/STAT1, and IL-12/STAT4) and the CD4{sup +} and CD8{sup +} populations in ileal mucosa and MLN during the first 3 months after 10 Gy abdominal irradiation. Results: The T-bet-deficient mice showed an increased fibrotic response to radiation, characterized by higher TGF-{beta}1, col3a1 expression, and collagen deposition in mucosa compared with wild-type mice. This response was associated with drastically lower expression of IFN-{gamma}, the hallmark Th1 cytokine. Analysis of the Th1 expression pathways, T-bet/STAT1 and IL-12/STAT4, showed their equal involvement in the failure of Th1 polarization. A minimal IFN-{gamma} level depended on the IL-23-p19/STAT4 level. In addition, the radiation-induced deficiency in the priming of Th1 by IFN-{gamma} was related to the defective homing capacity of CD8{sup +} cells in the mucosa. Conclusion: Irradiation induces Th2 polarization, and the Th2 immune response may play a role in potentiating irradiation-induced intestinal collagen deposition.

  20. The effect of feed supplementation with Zakarpacki zeolite (clinoptilolite) on percentages of T and B lymphocytes and cytokine concentrations in poultry.

    Science.gov (United States)

    Jarosz, Lukasz; Stepien-Pysniak, Dagmara; Gradzki, Zbigniew; Kapica, Malgorzata; Gacek, Agata

    2017-07-01

    The available literature lacks information on the effect of Zakarpacki zeolite (clinoptilolite) on the immune system of poultry. Therefore, the aim of this study was to determine the effect of this zeolite on selected indicators of the immune response in poultry by evaluating the expression of cluster of differentiation (CD) surface molecules on T and B lymphocytes and the concentration of IL-2 and IL-10 in the blood. Ninety one-day-old Ross 308 broiler chicks were used in the study. The birds were divided into 3 groups of 30 each. The same basic diet was used in all groups, but groups II and III received a feed additive in the form of 2% and 3% zeolite. Blood samples were collected from all birds on the 40th day of observations. Weight gain in the birds in both experimental groups was significantly higher, and no clinical symptoms of disease were observed. The percentage of CD4+CD25+ T and B lymphocytes was higher in both groups receiving zeolite, but the percentage of CD8+CD25+ T lymphocytes was higher only in the group receiving 3% zeolite. There were no differences between the groups in the percentage of cells with CD3+ and MHC Class II expression. Higher serum concentrations of IL-2 and IL-10 were noted only in group III. The use of zeolites enhances antigen presentation and leads to increased Th1 and Th2 response. Excessive supply of zeolite in the feed leads to a local inflammatory response, which may cause damage to the intestinal barrier. © 2017 Poultry Science Association Inc.

  1. Soluble ions more than particulate cobalt-alloy implant debris induce monocyte costimulatory molecule expression and release of proinflammatory cytokines critical to metal-induced lymphocyte reactivity.

    Science.gov (United States)

    Caicedo, Marco S; Pennekamp, Peter H; McAllister, Kyron; Jacobs, Joshua J; Hallab, Nadim J

    2010-06-15

    Aseptic osteolysis has been associated with excessive immune reactivity to particulate implant debris; however, innate and adaptive immune mechanisms that underlie implant debris reactivity remain incompletely understood. Although particulate debris has been implicated as the major type of implant debris mediating macrophage-induced osteolysis, the degree to which metal ions affect a proinflammatory response (if at all) remains unknown. We hypothesized that both soluble and particulate metal implant debris will induce proinflammatory responses in human monocytes resulting in cytokine production and elevated expression of T cell costimulatory molecules, facilitating adaptive immune responses. We tested this hypothesis by characterizing the response of a human monocyte cell line (THP-1), isolated primary human monocytes and PBMCs challenged with Co-Cr-Mo alloy particles and soluble cobalt, chromium, molybdenum, and nickel ions. Our results indicate that soluble cobalt, nickel, and molybdenum can induce monocyte up-regulation of T cell costimulatory molecules (CD80, CD86, ICAM-1) in human monocytes/macrophages. Furthermore, cobalt, molybdenum ions, and Co-Cr-Mo alloy particles similarly induce elevated secretion of IL-1beta, TNFalpha, and IL-6. Antibody blockade of CD80 and CD86, crucial secondary molecules for adaptive responses, abrogated lymphocyte reactivity to metal challenge in metal reactive subjects. Also the addition of IL-1 receptor antagonist (IL-1ra), (which indirectly blocks pro-IL-1beta and thus IL-1beta release), significantly reduced lymphocyte reactivity in metal-reactive subjects. Thus, both soluble and particulate metal implant debris induce monocyte/macrophage proinflammatory responses that are metal and individual specific. This suggests metal-induced up-regulation of costimulatory molecules and proinflammatory cytokine production is necessary to induce lymphocyte activation/proliferation to metal implant debris.

  2. An aza-anthrapyrazole negatively regulates Th1 activity and suppresses experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Clark, Matthew P; Leaman, Douglas W; Hazelhurst, Lori A; Hwang, Eun S; Quinn, Anthony

    2016-02-01

    Previously we showed that BBR3378, a novel analog of the anticancer drug mitoxantrone, had the ability to ameliorate ascending paralysis in MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis, without the drug-induced cardiotoxicity or lymphopenia associated with mitoxantrone therapy. Chemotherapeutic drugs like mitoxantrone, a topoisomerase inhibitor, are thought to provide protection in inflammatory autoimmune diseases like EAE by inducing apoptosis in rapidly proliferating autoreactive lymphocytes. Here, we show that while BR3378 blocked cell division, T cells were still able to respond to antigenic stimulation and upregulate surface molecules indicative of activation. However, in contrast to mitoxantrone, BBR3378 inhibited the production of the proinflammatory cytokine IFN-γ both in recently activated T cell blasts and established Th1 effectors, while sparing the activities of IL-13-producing Th2 cells. IFN-γ is known to be regulated by the transcription factor T-bet. In addition to IFN-γ, in vitro and in vivo exposure to BBR3378 suppressed the expression of other T-bet regulated proteins, including CXCR3 and IL-2Rβ. Microarray analysis revealed BBR3378-induced suppression of additional T-bet regulated genes, suggesting that the drug might disrupt global Th1 programming. Importantly, BBR3378 antagonized ongoing Th1 autoimmune responses in vivo, modulated clinical disease and CNS inflammation in acute and relapsing forms of EAE. Therefore, BBR3378 may be a unique inhibitor of T-bet regulated genes and may have potential as a therapeutic intervention in human autoimmune disease.

  3. A polysaccharide isolated from Agaricus blazei Murill (ABP-AW1) as a potential Th1 immunity-stimulating adjuvant.

    Science.gov (United States)

    Cui, Liran; Sun, Yongxu; Xu, Hao; Xu, Huiyu; Cong, Huan; Liu, Jicheng

    2013-10-01

    In the present study, a low molecular weight polysaccharide, ABP-AW1, isolated from Agaricus blazei Murill was assessed for its potential adjuvant activity. ABP-AW1 is considered to create a 'depot' of antigen at a subcutaneous injection site. ICR mice were immunized with 100 μg ovalbumin (OVA) alone or with 100 μg OVA formulated in 0.9% saline containing 200 μg aluminum (alum) or ABP-AW1 (50, 100 and 200 μg) on days 1 and 15. Two weeks after the secondary immunization, splenocyte proliferation, the expression of surface markers, cytokine production and the OVA-specific antibody levels in the serum were determined. The OVA/ABP-AW1 vaccine, in comparison with OVA alone, markedly increased the proliferation of splenic lymphocytes and elicited greater antigen-specific CD4(+) T cell activation, as determined by splenic CD4(+)CD69(+) T cells and Th1 cytokine interferon (IFN)-γ release. The combination of ABP-AW1 and OVA also enhanced IgG2b antibody responses to OVA. In conclusion, these data indicated that ABP-AW1 significantly enhanced the humoral and cellular immune responses against OVA in the mice, suggesting that ABP-AW1 stimulated Th1-type immunity. We suggest that ABP-AW1 may serve as a new adjuvant.

  4. Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway.

    Science.gov (United States)

    Neumann, Katrin; Rudolph, Christine; Neumann, Christian; Janke, Marko; Amsen, Derk; Scheffold, Alexander

    2015-07-01

    Under homeostasis, liver sinusoidal endothelial cells (LSECs) shift intrahepatic T-cell responses towards tolerance. However, the role of LSECs in the regulation of T-cell-induced liver inflammation is less clear. Here, we studied the capacity of LSECs to modulate pro-inflammatory Th1-cell differentiation in mice. Using in vitro co-culture systems and subsequent cytokine analysis, we showed that LSECs induced high amounts of the anti-inflammatory cytokine IL-10 in developing Th1 cells. These LSEC-stimulated Th1 cells had no pro-inflammatory capacity in vivo but instead actively suppressed an inflammatory Th1-cell-induced delayed-type hypersensitivity reaction. Blockage of IL-10 signaling in vivo inhibited immunosuppressive activity of LSEC-stimulated Th1 cells. We identified the Notch pathway as a mechanism how LSECs trigger IL-10 expression in Th1 cells. LSECs expressed high levels of the Delta-like and Jagged family of Notch ligands and induced expression of the Notch target genes hes-1 and deltex-1 in Th1 cells. Blockade of Notch signaling selectively inhibited IL-10 induction in Th1 cells by LSECs. Our findings suggest that LSEC-induced IL-10 expression in Th1 cells via the Notch pathway may contribute to the control of hepatic inflammatory immune responses by induction of a self-regulatory mechanism in pro-inflammatory Th1 cells.

  5. Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in patients with active rheumatoid arthritis: correlation with pharmacokinetic measures

    Science.gov (United States)

    Kremer, Joel M; Lawrence, David A; Hamilton, Robert; McInnes, Iain B

    2016-01-01

    Objective To describe changes in immune parameters observed during long-term methotrexate (MTX) therapy in patients with active rheumatoid arthritis (RA) and explore correlations with simultaneously measured MTX pharmacokinetic (PKC) parameters. Design Prospective, open-label, long-term mechanism of action study. Setting University clinic. Methods MTX was initiated at a single weekly oral dose of 7.5 mg and dose adjusted for efficacy and toxicity for the duration of the study. Standard measures of disease activity were performed at baseline and every 6–36 months. Serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell (PBMC) cytokine production were assessed at each clinical evaluation. Results Cytokine concentrations exhibited multiple significant correlations with disease activity measures over time. The strongest correlations observed were for interleukin (IL)-6 (r=0.45, p<0.0001 for swollen joints and r=0.32, p=0.002 for tender joints) and IL-8 (r=0.25, p=0.01 for swollen joints). Significant decreases from baseline were observed in serum IL-1B, IL-6 and IL-8 concentrations. The most significant changes were observed for IL-6 (p<0.001). Significant increases from baseline were observed in IL-2 release from PBMCs ex vivo (p<0.01). In parallel, multiple statistically significant correlations were observed between MTX PKC measures and immune parameters. The change in swollen joint count correlated inversely with the change in area under the curve (AUC) for MTX (r=−0.63, p=0.007). Conclusions MTX therapy of patients with RA is accompanied by a variety of changes in serum cytokine expression, which in turn correlate strongly with clinical disease activity and MTX pharmacokinetics (PKCs). These data strongly support the notion that MTX mediates profound and functionally relevant effects on the immunological hierarchy in the RA lesion. PMID:27335660

  6. Effect of cyclosporine, dexamethasone, and human CTLA4-Ig on production of cytokines in lymphocytes of clinically normal cats and cats undergoing renal transplantation.

    Science.gov (United States)

    Aronson, Lillian R; Stumhofer, Jason S; Drobatz, Kenneth J; Hunter, Christopher A

    2011-04-01

    To evaluate effects of cyclosporine, dexamethasone, and the immunosuppressive agent human CTLA4-Ig on cytokine production by feline lymphocytes in vitro and to assess patterns of cytokine production for 5 immunosuppressed renal transplant recipient cats. 21 clinically normal cats and 5 immunosupressed renal transplant recipient cats. Peripheral blood mononuclear cells were isolated from clinically normal cats and stimulated with concanavalin A (Con A; 10 μg/mL) alone or Con A with cyclosporine (0.05 μg/mL), dexamethasone (1 × 10(-7)M), a combination of cyclosporine-dexamethasone, or human CTLA4-Ig (10 g/mL). Cells from transplant recipients were stimulated with Con A alone. An ELISA was performed to measure production of interferon (IFN)-γ, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, and IL-10. Proliferation of CD4+ and CD8+T cells from immunosuppressed cats were also evaluated. Pairwise comparisons were performed via a Wilcoxon signed rank test or Wilcoxon rank sum test. Cyclosporine, dexamethasone, cyclosporine-dexamethasone combination, and CTLA4-Ig caused a significant decrease in IL-2, IFN-γ, and GM-CSF production. Cyclosporine and cyclosporine-dexamethasone, but not human CTLA4-Ig, caused a significant decrease in IL-10 production. High basal concentrations of IL-2 and IL-10 were identified in transplant recipients, and IL-10 was significantly increased in stimulated cultures. In immunosuppressed cats, there was a decrease in frequency of responders and proliferative capacity of CD4+ and CD8+T cells. CTLA4-Ig successfully inhibited proinflammatory cytokines while sparing cytokines critical for allograft tolerance. These data may be useful for developing better strategies to prevent rejection while sparing other immune functions.

  7. T Lymphocyte Autoreactivity in Inflammatory Mechanisms Regulating Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Elisabetta Profumo

    2012-01-01

    Full Text Available Atherosclerosis has been clearly demonstrated to be a chronic inflammatory disease of the arterial wall. Both cells of the innate and the acquired immune system, particularly monocytes and T lymphocytes, are implicated in the atherogenic process, producing different cytokines with pro- and anti-inflammatory effects. The majority of pathogenic T cells involved in atherosclerosis are of the Th1 profile, that has been correlated positively with coronary artery disease. Many studies conducted to evaluate the molecular factors responsible for the activation of T cells have demonstrated that the main antigenic targets in atherosclerosis are modified endogenous structures. These self-molecules activate autoimmune reactions mainly characterized by the production of Th1 cytokines, thus sustaining the inflammatory mechanisms involved in endothelial dysfunction and plaque development. In this paper we will summarize the different T-cell subsets involved in atherosclerosis and the best characterized autoantigens involved in cardiovascular inflammation.

  8. Cytokine profiling of tumor interstitial fluid of the breast and its relationship with lymphocyte infiltration and clinicopathological characteristics

    DEFF Research Database (Denmark)

    Espinoza, Jaime A.; Jabeen, Shakila; Batra, Richa

    2016-01-01

    normal interstitial fluid (NIF) samples, and 25 matched serum samples obtained from BC patients with Luminex xMAP multiplex technology. Eleven cytokines exhibited significantly higher levels in the TIF samples compared with the NIF samples: interleukin (IL)-7, IL-10, fibroblast growth factor-2, IL-13...

  9. Myostatin expression, lymphocyte population, and potential cytokine production correlate with predisposition to high-fat diet induced obesity in mice.

    Directory of Open Access Journals (Sweden)

    Jeri-Anne Lyons

    Full Text Available A strong relationship exists between increased inflammatory cytokines and muscle insulin resistance in obesity. This study focused on identifying a relationship between metabolic propensity and myostatin expression in muscle and spleen cells in response to high-fat diet intake. Using a comparative approach, we analyzed the effects of high-fat diet intake on myostatin and follistatin expression, spleen cell composition, and potential cytokine expression in high-fat diet induced obesity (HFDIO resistant (SWR/J and susceptible (C57BL/6 mice models. Results demonstrated overall increased myostatin expression in muscle following high-fat diet intake in HFDIO-susceptible mice, while myostatin expression levels decreased initially in muscle from high-fat diet fed resistant mice. In HFDIO-resistant mice, myostatin expression decreased in spleen, while myostatin increased in spleen tissue from HFDIO-susceptible mice. Proinflammatory cytokine (IL-17, IL-1β, and IFNγ potential increased in splenocytes from HFDIO-susceptible mice. In comparison, C57BL/6 mice fed a high-fat diet exhibited higher frequencies of CD4(+/CD44(hi and CD8(+/CD44(hi cells in the spleen compared to control fed mice. Together, these results suggest that susceptibility to high-fat diet induced obesity could be influenced by local myostatin activity in a tissue-specific manner and that splenocytes exhibit differential cytokine production in a strain-dependent manner. This study sets the stage for future investigations into the interactions between growth, inflammation, and metabolism.

  10. Ulmus davidiana var. japonica Nakai upregulates eosinophils and suppresses Th1 and Th17 cells in the small intestine.

    Directory of Open Access Journals (Sweden)

    Han-Sung Lee

    Full Text Available The bark of Ulmus davidiana var. japonica Nakai (Ulmaceae has been used in traditional Korean medicine for chronic inflammation in the gastrointestinal tract. Here we investigated the frequency and cytokine profile of the major immune cells in the small intestinal lamina propria (SI LP, spleen, and mesenteric lymph nodes (MLNs of mice treated orally with Ulmus davidiana var. japonica Nakai bark water extract (UDE to address the immunomodulatory role of this herb in intestinal homeostasis. B6 mice were given 5g/kg UDE once daily for 14 days. They were then sacrificed, and cells were isolated from the spleen, MLNs, and SI LP. The proportion of B versus T lymphocytes, CD4(+ versus CD8(+ T lymphocytes, Th1 and Th17 cells, and Foxp3(+ regulatory T cells in the spleen, MLNs, and SI LP were analyzed. The frequency of antigen-presenting cells (APCs, including dendritic cells, macrophages, and eosinophils in the SI LP and the expression of costimulatory molecules on APCs were also evaluated. The numbers and frequencies of Th1 and Th17 cells in the SI LP were significantly reduced in the UDE-treated mice compared with PBS controls. In addition, the proportion of IL-4-producing eosinophils in the SI LP was significantly elevated in the UDE-treated mice compared with controls. Taken together, these data indicate that UDE up-regulates the number and frequency of SI LP eosinophils, which can down-regulate the Th1 and Th17 responses via IL-4 secretion and contribute to intestinal homeostasis.

  11. Effect of different anesthesia and analgesia methods on theT lymphocyte subsets, cytokines and stress hormone level in patients with breast cancer surgery

    Institute of Scientific and Technical Information of China (English)

    Yan Ma; Xi-Qiang He; Geng Wang

    2015-01-01

    Objective: To explore the effect of different anesthesia and analgesia methods on the T lymphocyte subsets, cytokines and the levels of the stress hormone in patients with breast cancer surgery.Methods: 86 cases of breast cancer were divided into two groups by random digits table, control group of 43 cases with total intravenous anesthesia, and the observation group of 43 cases with total intravenous anesthesia combined with epidural anesthesia and postoperative underwent analgesia. The T lymphocyte subsets, cytokines and the levels of the stress hormone were detected before and after operation and compared. Results:CD3+, CD4+ and CD4+/CD8+ of the two groups at T1 or T2 were significantly lower than those at T0, and those in the observation group were significantly lower than the control group, and the difference between the two groups has statistical significance. IL-6, CRP and TNF-α levels of the two groups at T1, T2 or T3 were significantly higher than those at T0, and those in the observation group were significantly lower than the control group, and the difference between the two groups has statistical significance. Each index of two groups at T4 were restored to T0, and the differences were no statistically significant. The cortisol levels of two groups at T1 or T2 were significantly increased compared with T0, and the increase in the observation group was less than that of the control group, the difference between the two groups has statistical significance. The cortisol levels of two groups at T4 were restored to T0, and the differences were no statistically significant.Conclusion:Epidural analgesia after the intravenous anesthesia combined with epidural anesthesia for breast cancer cure patients has lighter immunosuppression and stress reaction, has less influence on inflammatory factors, is an ideal anesthesia and analgesia.

  12. Cytokines and Epstein Barr virus (EBV) genes expression in blood chronic lymphocytic leukaemia (CLL) cells and their immortalised CLL cell lines.

    Science.gov (United States)

    Laytragoon-Lewin, Nongnit; Chen, Fu; Castro, Juan; Avila-Carino, Javier; Lewin, Freddi

    2003-01-01

    We have encountered two unique chronic lymphocytic leukaemia (CLL) patients, PG and NN. Some blood CLL cells of these patients have been infected and carry Epstein Barr virus (EBV) in vivo. In spite of their early-activated G0/G1 stage of post germinal center (GC) memory cells, ex vivo EBV-carrying blood CLL cells of PG clone expressed LMPs and used specific QUK splice for their EBNA1 expression, similar to the EBV-carrying cells of non-B origin. Interestingly, EBV-carrying CLL cells of NN clone expressed LMP2a and used UK-splice for their EBNA1 expression, similar to the in vivo EBV-carrying high density normal B cells in the blood of healthy individuals. The CLL-derived lines but not normal lymphoblastoid cell line (LCL) used QUK- and YUK-splice for their EBNA1 expression. As expected, LCL and their permanent CLL-derived lines used Cp promoter and up-regulated their EBNA2 expression. Blood CLL cells and the CLL-derived cell lines of these patients spontaneously produced cytokines as shown by microarray assay. The types and quantities of cytokines might relate to their CLL origin and viral strain in the given CLL cells. Neither blood CLL nor their CLL-derived cell lines express any detectable apoptosis-inducer ligands, CD95L or Apo 3L. As a consequence of cell cycle progression, CLL-derived cell lines up-regulated their co-stimulator molecules CD80 and apoptosis-related receptor CD95. Since only the rare EBV-carrying CLL cells grew in vitro, the combination of viral genome and cytokines seems to be critical for the outgrowth of EBV-carrying CLL cells over their EBV-negative counterpart in vitro but not in vivo.

  13. Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis.

    Science.gov (United States)

    Hernández-Pando, R; Orozcoe, H; Sampieri, A; Pavón, L; Velasquillo, C; Larriva-Sahd, J; Alcocer, J M; Madrid, M V

    1996-01-01

    T-helper 1 (Th1) Th2 kinetics were studied by immunohistochemistry and molecular biology techniques (reverse transcriptase polymerase chain reaction. RT PCR, Southern-blot) during the course of pulmonary tuberculosis induced in BALB/c mice by the intratracheal instillation of the live and virulent strain H-37Rv. The histopathological study clearly showed two phases of the disease. The first one was an acute phase which was characterized by inflammatory infiltrate in the alveolar capillary interstitium, blood vessel and bronchial wall with formation of granulomas. In this acute phase which lasted from 1 to 28 days, a clear predominance of Th1 cells was observed, manifested by a high percentage of interleukin-2 (IL-2) positive cells in the inflammatory infiltrate and granulomas demonstrated by immunohistology, as well as a gradual increment of interferon-gamma (INF-gamma) m-RNA. This was followed by a chronic or advanced phase characterized by pneumonia, focal necrosis and fibrosis, with a Th0 balance due to an equivalent proportion of IL-2 and IL-4 positive cells in the lung lesions, that coincided with the highest level of INF-gamma and IL-4 mRNA. The cytofluorometric analysis of bronchial lavage cells, showed a predominance of CD4 T cells during the acute phase and CD8 T lymphocytes in the chronic phase, gamma-delta T lymphocytes showed two peaks, at the beginning (3 days) and at the end (4 months) of the infection. These results suggest that T-lymphocyte subset kinetics and the pattern of cytokines produced in the lung during tuberculosis infection changed over time and correlate with the type and magnitude of tissue injury. Images Figure 1 Figure 3 Figure 5 PMID:8911136

  14. Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Age-related impaired T cell function is associated with increased mortality risk. The purpose of the present study was therefore to identify factors associated with the age-related decreased phytohaemagglutinin (PHA)-induced proliferative response of lymphocytes in a cohort of 174 81-year......-old humans and in 91 young controls. Decreased proliferation was associated with a reduced number of true naive CD4(+) cells (CD62L(+)CD45RO(-)). Furthermore, a low IL-2-stimulated proliferation was correlated with a decreased PHA response in the elderly cohort, whereas reciprocal interactions of IL-10......- and IL-2-producing cells were of importance in both elderly and young subjects. Accordingly, a minimum of true naive CD4(+) cells was required for a normal proliferative response to PHA, perhaps by providing sufficient IL-2 which is critical for growth of naive as well as memory cells....

  15. Toll-Like Receptor 7 Agonist Therapy with Imidazoquinoline Enhances Cancer Cell Death and Increases Lymphocytic Infiltration and Proinflammatory Cytokine Production in Established Tumors of a Renal Cell Carcinoma Mouse Model

    Directory of Open Access Journals (Sweden)

    Eric C. Kauffman

    2012-01-01

    Full Text Available Imidazoquinolines are synthetic toll-like receptor 7 and 8 agonists and potent dendritic cell activators with established anticancer activity. Here we test the hypothesis that imidazoquinoline has in vivo efficacy within established renal cell carcinoma (RCC tumors. Immunocompetent mice bearing syngeneic RCC xenografts were treated with imidazoquinoline or placebo at two separate time points. Harvested tumors were assayed by TUNEL/caspase-3/Ki67 immunostains to evaluate cell death/apoptosis/proliferation, and CD3/B220/CD45 immunostains to evaluate T-cell lymphocyte/B-cell lymphocyte/pan-leukocyte tumor infiltration. ELISA measurement of tumor and serum levels of proinflammatory cytokines, IL-6 and MCP-1, was performed. A single imidazoquinoline dose significantly decreased RCC tumor growth by 50% and repeat dosing compounded the effect, without observed weight loss or other toxicity. Tumor immunostaining revealed significant increases in cell death and apoptosis without changes in cell proliferation, supporting induction of apoptosis as the primary mechanism of tumor growth suppression. Imidazoquinoline treatment also significantly enhanced peritumoral aggregation and intratumoral infiltration by T-cell lymphocytes, while increasing intratumoral (but not serum levels of proinflammatory cytokines. In conclusion, imidazoquinoline treatment enhances T-cell lymphocyte infiltration and proinflammatory cytokine production within established mouse RCC tumors, while suppressing tumor growth via induction of cancer cell apoptosis. These findings support a therapeutic role for imidazoquinoline in RCC.

  16. The effects of the expression of cytokines on Th1/Th2 balance in intestinal mucosa of TNBS induced experimental rat colitis and regulation of VSL#3%实验性结肠炎大鼠结肠黏膜中炎性因子对Th1/Th2平衡的影响及VSL#3的调节作用

    Institute of Scientific and Technical Information of China (English)

    杨立; 李艳; 任秋华; 邢昱; 王岩; 姚远

    2014-01-01

    目的 观察益生菌VSL#3对减轻TNBS诱导的大鼠急性结肠炎结肠黏膜中IL-4、IL-13、IFN-γ、IL-12表达对Th1/Th2平衡的影响以及益生菌VSL#3的调节作用.方法 30只大鼠随机分为正常对照组、模型组、美沙拉嗪组、VSL#3组、美沙拉嗪+VSL#3组,建立TNBS大鼠结肠炎模型.观察各组大鼠一般情况、排便情况、组织病理学变化及Th 1/Th2表达情况.取结肠组织做HE染色,观察病理学改变;酶联免疫吸附试验(ELISA)检测肠组织髓过氧化物酶(MPO)的变化;逆转录聚合酶链反应(RT-PCR)及Western blotting法检测各组大鼠结肠黏膜组织中IL-4、IL-13、IFN-γ、IL-12的表达.结果 与TNBS模型组比较,VSL#3组、美沙拉嗪组、VSL#3+美沙拉嗪组大鼠的疾病活动指数评分(DAI)、肠组织MPO水平、结肠炎大鼠病理评分均降低.RT-PCR及Western blotting检测发现:与TNBS组相比,VSL#3组、美沙拉嗪组和VSL#3+美沙拉嗪组均可下调促炎因子IL-12、IFN-γ的表达,上调抗炎因子IL-4、IL-13的表达,VSL#3组与美沙拉嗪组比较,差异无统计学意义(P>0.05).Th1/Th2的比值依如下顺序减少:TNBS模型组>VSL#3组>美沙拉嗪组>美沙拉嗪+ VSL#3>正常对照组,其比值逐渐趋于正常对照组.结论 VSL#3对TNBS诱导的大鼠实验性结肠炎有治疗作用,其作用机制可能与下调IFN-γ、IL-12,上调IL-4、IL-13炎性因子的表达,使Th1/Th2的平衡趋于正常有关.

  17. Serum Levels of IL-6 Type Cytokines and Soluble IL-6 Receptors in Active B-Cell Chronic Lymphocytic Leukemia and in Cladribine Induced Remission

    Directory of Open Access Journals (Sweden)

    T. Robak

    1999-01-01

    Full Text Available We have investigated the serum concentrations of interleukin-6 (IL-6 and two IL-6 family cytokines-oncostatin M (OSM and leukemia inhibitory factor (LIF-in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL and 17 healthy controls using the enzyme-linked immunosorbent assay (ELISA method. Simultaneously, we measured the serum levels of the soluble forms of two subunits of the IL-6 receptor complex-ligand binding glycoprotein 80 (sIL-6R and glycoprotein 130 (sgp130. The cytokines and receptors were evaluated in 25 untreated patients and 38 patients treated with cladribine (2-CdA, as well as in 17 healthy controls. We have correlated the serum levels of these proteins with Rai's clinical stage of the disease, the response to 2-CdA treatment and some hematological parameters. We have also evaluated the correlation of the IL-6 serum level with the concentration of OSM and IL-6 soluble receptors. IL-6 was measurable in 62/63 (98.4%, OSM in 20/25 (80% of untreated and 14/38 (37.8% of the treated patients. sIL-6R and sgp130 were detectable in all 63 patients and LIF in none of the CLL patients. IL-6 serum level in untreated patients was not significantly different as compared to its concentration in the control group (P>0.05. However, in the patients treated with 2-CdA the IL-6 level was significantly lower (P0.05. We have found significant positive correlation between the levels of sIL6R and the lymphocytes count in CLL patients (Ρ=0.423; P<0.001. In addition, sIL-6R and OSM serum concentrations correlated also with CLL Rai stage. In conclusion, the serum level of IL-6, OSM and sIL-6R, but not LIF and sgp130, are useful indicators of CLL activity.

  18. Effect of compound glycyrrhizin combined with NB-UVB on T lymphocyte subsets and related cytokines in patients with psoriasis vulgaris

    Institute of Scientific and Technical Information of China (English)

    Zhi-Feng Yue; Xue-Song Han; Dong Yin; Kun Tian; Xing Guo; Xiao-Dan Liu

    2016-01-01

    Objective:To explore the effect of compound glycyrrhizin in combined with narrow band ultraviolet B (NB-UVB) on T lymphocyte subsets and related cytokines in patients with psoriasis vulgaris.Methods:A total of 70 patients with psoriasis vulgaris who were admitted in our hospital from March, 2015 to March, 2016 were included in the study and randomized into the study group and the control group. The patients in the control group were given NB-UVB for whole body irradiation, with an initial dose of 0.3 J/cm2, 0.2-0.3 J/cm2 increased every time, 3 times a week. On this basis, the patients in the study group were intravenously injected with compound glycyrrhizin (80 mg) + 5% glucose (250 mL), 1 time a day. Four-week treatment was regarded as one course. ELISA was used to detect the serum IL-17 and IL-22 levels. FCM was used to detect the levels of peripheral blood T lymphocytes (CD4+, CD8+, CD4+/CD8+). PASI score before and after treatment was evaluated.Results:The levels of IL-17 and IL-22 after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05), and the reduced degree in the study group was significantly superior to that in the control group (P<0.05). The levels of CD4+ and CD4+/CD8+ after treatment in the two groups were significantly elevated, but CD8+ was significantly reduced when compared with before treatment (P<0.05), and those in the study group were significantly superior to those in the control group (P<0.05). PASI score after treatment in the two groups was significantly reduced when compared with before treatment (P<0.05), and the reduced degree in the study group was significantly superior to that in the control group (P<0.05). Conclusions: Compound glycyrrhizin in combined with NB-UVB in the treatment of psoriasis vulgaris can effectively down regulate the cytokine level, recover T cell immune function, and improve PASI score; therefore, it deserves to be widely recommended in the clinic.

  19. Repressor of GATA-3 can negatively regulate the expression of T cell cytokines through modulation on inducible costimulator

    Institute of Scientific and Technical Information of China (English)

    ZANG Yuan-sheng; FANG Zheng; LIU Yong-an; LI Bing; XIU Qing-yu

    2012-01-01

    Background The transcription factor,repressor of GATA-3 (ROG),can simultaneously suppress the expression of T helper cells (Th1 and Th2) cytokines.Since the suppression of Th2 cytokines by GATA-3 is well understood,it is postulated that there are other molecular targets of ROG that can suppress the expression of the Th1 cytokines.We hypothesized that ROG might suppress the stimulators of T lymphocyte cytokines such as CD3,CD28,and inducible costimulator (ICOS),or indirectly enhance the expression of cytokine suppressors such as T lymphocyte-associated antigen-4 (CTLA-4) and CD45.The objective of this study was to clarify the molecular targets of ROG involved in suppressing Th1 or Th2 cytokines.Methods Real-time quantitative PCR (RT-PCR) and Westem blotting were performed to evaluate the mRNA and protein levels of CD3,CD28,ICOS,CTLA-4,and CD45 in Th1 and Th2 cells during vadous levels of ROG expression.Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interferon-y (IFN-y) and intedeukin (IL)-4 in culture media of Th1 and Th2 cells.Results The results showed that the mRNA and protein levels of ROG were relatively low in Th1 and Th2 cells (P<0.01).After ROG-pcDNA3.1 transfection,the mRNA and protein level of ROG was significantly elevated,while the expression of ICOS,IFN-y,and IL-4 was markedly down-regulated (P <0.01 ).Conversely,transfection of ROG-siRNA led to inhibition of ROG expression and up-regulation of ICOS,IFN-y and IL-4 (P <0.01).However,the expression levels of CD3,CD28,CTLA-4 and CD45 did not change in either ROG-pcDNA3.1 or ROG-siRNA-transfected Th1 and Th2 cells (P>0.05).Conclusion It is concluded that ROG can inhibit the expression of Th1 and Th2 cytokines by down-regulating the expression of ICOS,which might be a potential molecular target for asthma treatment.

  20. Effects of polyphenols including curcuminoids, resveratrol, quercetin, pterostilbene, and hydroxypterostilbene on lymphocyte pro-inflammatory cytokine production of senior horses in vitro.

    Science.gov (United States)

    Siard, Melissa H; McMurry, Kellie E; Adams, Amanda A

    2016-05-01

    quercetin and resveratrol. Flunixin meglumine and phenylbutazone were then evaluated within this range of optimal concentrations for the polyphenol compounds (160, 80, 40, 20 μM) to compare the polyphenols to NSAIDs at equivalent concentrations. The highest concentration at which viability did not significantly differ from the positive control was: 40 μM for flunixin meglumine and 160 μM for phenylbutazone. All five polyphenols and flunixin meglumine significantly decreased lymphocyte production of IFN-γ, while only hydroxypterostilbene, pterostilbene, quercetin, and resveratrol significantly reduced lymphocyte production of TNF-α compared to the positive control (p Polyphenols performed similarly to or more effectively than common NSAIDs in reducing lymphocyte production of inflammatory cytokines of the senior horse in vitro. This study therefore supports the further investigation of polyphenols to determine whether they may be effective anti-inflammatory treatments for chronic inflammation in the horse.

  1. Th1 and Th2 immune response to P30 and ROP18 peptides in human toxoplasmosis.

    Science.gov (United States)

    Torres-Morales, Elizabeth; Taborda, Laura; Cardona, Nestor; De-la-Torre, Alejandra; Sepulveda-Arias, Juan Carlos; Patarroyo, Manuel Alfonso; Gomez-Marin, Jorge Enrique

    2014-10-01

    We determined the specific lymphocyte proliferative response and cytokine profile production regarding Toxoplasma P30 (2017 from virulent and non-virulent strain) and ROP18 protein-derived peptides (from clonal lineages I, II and III) in 19 patients having ocular toxoplasmosis, five suffering chronic asymptomatic infection, nine with congenital toxoplasmosis and eight Toxoplasma negative people. A Beckman Coulter FC500 flow cytometer was used for determining antigen-specific T cells (CD3+ CD4+ or CD3+ CD8+ cells) in peripheral blood culture. IFN γ and IL10 levels were determined in culture supernatants. Specific CD4+ and CD8+ T cell response to total antigen and P30- and ROP18-derived peptides was observed in infected people. Ocular toxoplasmosis patients had a preferential Th2 response after antigenic stimulation. Non-virulent peptide 2017 was able to shift response toward Th1 in congenitally infected children and virulent peptide 2017 induced a Th2 response in chronically infected, asymptomatic people. An immune response in human toxoplasmosis after ex vivo antigenic stimulation was Th1- or Th2-skewed, depending on a patient's clinical condition. Colombian ocular toxoplasmosis patients' immune response was Th2-skewed, regardless of the nature of antigen stimulus.

  2. Mycobacterium tuberculosislpdC, Rv0462, induces dendritic cell maturation and Th1 polarization

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Deok Rim [Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Shin, Sung Jae; Kim, Woo Sik [Department of Microbiology, College of Medicine, Chungnam National University, Munwha-Dong, Jung-Ku, Daejeon 301-747 (Korea, Republic of); Noh, Kyung Tae; Park, Jin Wook; Son, Kwang Hee [Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Park, Won Sun [Department of Physiology, Kangwon National University, School of Medicine, Chuncheon 200-701 (Korea, Republic of); Lee, Min-Goo [Department of Physiology, Korea University, College of Medicine, Anam-dong, Sungbuk-Gu, Seoul 136-705 (Korea, Republic of); Kim, Daejin [Department of Anatomy, Chung-Ang University, College of Medicine, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Shin, Yong Kyoo [Department of Pharmacology, Chung-Ang University, College of Medicine, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Jung, In Duk, E-mail: jungid@pusan.ac.kr [Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Park, Yeong-Min, E-mail: immunpym@pusan.ac.kr [Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of)

    2011-08-05

    Highlights: {yields} Treatment with Rv0462 induces the expression of surface molecules and the production of cytokines in DCs. {yields} Rv0462 induces the activation of MAPKs. {yields} Rv0462-treated DCs enhances the proliferation of CD4{sup +} T cells. -- Abstract: Mycobacterium tuberculosis, the etiological factor of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). In this study, we demonstrated that the gene encoding lipoamide dehydrogenase C (lpdC) from M. tuberculosis, Rv0462, induce maturation and activation of DCs involved in the MAPKs signaling pathway. Moreover, Rv0462-treated DCs activated naive T cells, polarized CD4{sup +} and CD8{sup +} T cells to secrete IFN-{gamma} in syngeneic mixed lymphocyte reactions, which would be expected to contribute to Th1 polarization of the immune response. Our results suggest that Rv0462 can contribute to the innate and adaptive immune responses during tuberculosis infection, and thus modulate the clinical course of tuberculosis.

  3. Polysaccharides from Ganoderma formosanum function as a Th1 adjuvant and stimulate cytotoxic T cell response in vivo.

    Science.gov (United States)

    Pi, Chia-Chen; Chu, Ching-Liang; Lu, Chu-Ying; Zhuang, Yu-Jing; Wang, Cheng-Li; Yu, Yao-Hsuan; Wang, Hui-Yi; Lin, Chih-Chung; Chen, Chun-Jen

    2014-01-09

    The fungus of Ganoderma is a basidiomycete that possesses a variety of pharmacological effects and has been used in traditional Asian medicine for centuries. Ganoderma formosanum is a native Ganoderma species isolated in Taiwan, and we have previously demonstrated that PS-F2, a polysaccharide fraction purified from the submerged culture broth of G. formosanum, exhibits immunostimulatory properties in macrophages. In this study, we further characterized the adjuvant functions of PS-F2. In vitro, PS-F2 stimulated dendritic cells (DCs) to produce proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-12/IL-23 p40. PS-F2 also stimulated DCs to express the maturation markers CD40, CD80, CD86, and MHC class II. In a murine splenocyte culture, PS-F2 treatment resulted in elevated expression of T-bet and interferon (IFN)-γ in T lymphocytes. When used as an adjuvant in vivo with the ovalbumin (OVA) antigen, PS-F2 stimulated OVA-specific antibody production and primed IFN-γ production in OVA-specific T lymphocytes. PS-F2-adjuvated immunization also induced OVA-specific CTLs, which protected mice from a challenge with tumor cells expressing OVA. Collectively, our data show that PS-F2 functions as an adjuvant capable of inducing a Th1-polarized adaptive immune response, which would be useful in vaccines against viruses and tumors.

  4. Th1 Th2, Tc1 Tc2 cells of patients with otolaryngological diseases

    Directory of Open Access Journals (Sweden)

    Nobuo Ohta

    2004-01-01

    Full Text Available Cytokines are important regulatory mediators secreted by T cells and other immunoactive cells. Based on the cytokine synthesis patterns, CD4 T cells can often be classified into at least two populations with different immune regulatory functions. The Th1 cells, producing interleukin (IL-2 and interferon (IFN-γ, are often associated with cell-mediated immune responses such as delayed type hypersensitivity (DTH, whereas Th2 cells, secreting IL-4, IL-5 and IL-13, usually provide B cell help and enhance allergic reactions. Naïve CD8 T cells, similar to CD4 T cells, can differentiate into at least two subsets of cytolytic effector cells with distinct cytokine patterns. The Tc1 cells secrete a Th 1 - like cytokine pattern, including IL-2 and IFN-γ. The Tc2 cells produce Th2 cytokines, including IL-4, IL-5 and 11—10. There is increasing evidence that Th1/Th2 and Tc1/Tc2 cytokine imbalance has been of patho- genetic importance in various diseases, such as allergic and autoimmune diseases. The present review article focuses on the evidence that the imbalance of Th1/Th2 and Tc1/Tc2 cytokines plays an important role in various otolaryngological diseases, such as Kimura's disease, Wegener's granulomatosism, acute perceptive hearing loss and Meniere's disease. It is concluded that the predominance of Th 1 or Th2 and Tc1 or Tc2 cells may contribute to the mechanism in the pathogenesis of these otolaryngological diseases.

  5. Effects of Neuromedin S on the Proliferation of Splenic Lymphocytes and the Cytokine Secretion by Pulmonary Alveolar Macrophages in Pigs in vitro.

    Science.gov (United States)

    Lin, R; Wang, Q; Qi, B; Huang, Y; Yang, G

    2016-09-01

    Neuromedin S (NMS), a 36-amino acid neuropeptide, has been found to be involved in the regulation of the endocrine activity. It has been also detected in immune tissues in mammals, what suggests that NMS may play an important role in the regulation of immune response. The aim of this study was to demonstrate the presence of NMS receptor 1 (NMU1R) and effect of NMS in pig splenic lymphocytes (SPLs) and pulmonary alveolar macrophages (PAMs). The presence of NMU1R in pig SPLs and PAMs was respectively confirmed by reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunocytochemical methods. Furthermore, SPL proliferation was analyzed using the 3-(4,5)-dimethyl-thiahiazo-(-2-yl)-3,5-di-phenytetrazoliumromide (MTT) method. Additionally, the secretion of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in PAMs was all measured by enzyme-linked immunosorbent assay (ELISA) kits. In the present study, the results of RT-PCR and western blot analysis revealed that NMU1R mRNA and protein were both expressed in pig SPLs and PAMs, and the immunocytochemical investigations further revealed that the positive signal of NMU1R immunoreactivity was observed in plasma membranes of both SPLs and PAMs. In the in vitro study, we found that at concentrations of 0.001-1000 nM NMS alone or combined with lipopolysaccharide or phytohemagglutinin significantly increased SPL proliferation. Application of ELISA method showed that NMS could induce the secretion of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in PAMs. These results suggest that NMS can act as a potently positive pro-inflammatory factor and immunomodulatory agent that affects the immune response of immune cells by combining with its receptor NMU1R.

  6. The Expression and Significance of Helper T Lymphocyte 1 and 2 Type Cytokines before and after Breast Cancer Surgery%乳腺癌手术前后辅助性T淋巴细胞1、2型细胞因子的表达及意义

    Institute of Scientific and Technical Information of China (English)

    岳雁鸿; 孙治君

    2011-01-01

    Objective To investigate the expression and significance of helper T lymphocyte (Th) 1 and 2 of breast cancer patients in vivo before and after operatioa Methods From November 2009 to December 2010, Thl-type cytokines [ interleukin-2 (IL-2), interferon-y (IFN-y)] and Th2-type cytokines ( IL-4, IL-6) expression in supernatants of peripheral blood mononuclear cells (PBMC) were detected by enzyme-linked immunosorbent assay (ELISA) in 40 breast cancer patients before and after surgery (Breast cancer group) and 15 healthy women (Control group). Results The test results of IL-2, IFN-y, IL-4 and IL-6 in peripheral blood for patients of breast cancer group were (326. 5+67. 4), (288. 5±35. 6), (41. 2+10. 8), and (526. 1±136. 4) ng/L before surgery, and (958.1±284. 7), (559.6+106.9), (26. 1±8.7), and (395.6+125.9) ng/L after surgery. Those results for patients in the normal control group were (1498. 0±325. 9), (784. 6+126. 3), (16. 6±3. 7), and (297. 4±83. 7) ng/L respectively. Compared with the control group, the expression of peripheral blood Thl-type cytokines in pre-operative breast cancer patients was significantly lower, while expression of Th2-type cytokines was significantly higher (P < 0. 05 ); Compared with the pre-operative data, the expression of peripheral blood Thl-type cytokines in post-operative breast cancer patients was significantly higher, and the expression of Th2-type cytokines was significantly lower (F<0. 05). Conclusions①For Th cells in breast cancer patients, there is a tendency of Thl suppression and Th2 polarization, and cellular immunity is suppressed. ② To some extent, surgical removal of tumors can reverse the Thl/Th2 imbalance early, improve the immune status, and has a positive effect on the prognosis.%目的 观察手术前后乳腺癌患者体内辅助性T淋巴细胞(helper Tlymphocyte,Th)1、2型细胞因子的表达及意义.方法 2009年11月-2010年12月,采用酶联免疫吸附试验检测40例乳腺癌患者(

  7. Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

    Institute of Scientific and Technical Information of China (English)

    Li-Fei; Yuan; Guang-Da; Li; Xin-Jun; Ren; Hong; Nian; Xiao-Rong; Li; Xiao-Min; Zhang

    2015-01-01

    · AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

  8. Uncaria tomentosa aqueous-ethanol extract triggers an immunomodulation toward a Th2 cytokine profile.

    Science.gov (United States)

    Domingues, Alexandre; Sartori, Alexandrina; Valente, Ligia Maria Marino; Golim, Marjorie Assis; Siani, Antonio Carlos; Viero, Rosa Marlene

    2011-08-01

    Uncaria tomentosa (Willd.) DC (Rubiaceae) is a large woody vine that is native to the Amazon and Central American rainforests and is used widely in traditional medicine for its immunomodulatory and antiinflammatory activities. The present work used in vivo immunotoxic and in vitro immunomodulatory experiments to investigate the effects of a pentacyclic oxindole alkaloid extract from U. tomentosa bark on lymphocyte phenotype, Th1/Th2 cytokine production, cellular proliferation and cytotoxicity. For the in vivo immunotoxicity testing, BALB/c male mice were treated once a day with 125, 500 or 1250 mg/kg of U. tomentosa extract for 28 days. For the in vitro protocol, lymphocytes were cultured with 10-500 μg/mg of the extract for 48 h. The extract increased the cellularity of splenic white pulp and the thymic medulla and increased the number of T helper lymphocytes and B lymphocytes. Also, a large stimulatory effect on lymphocyte viability was observed. However, mitogen-induced T lymphocyte proliferation was significantly inhibited at higher concentrations of U. tomentosa extract. Furthermore, an immunological polarization toward a Th2 cytokine profile was observed. These results suggest that the U. tomentosa aqueous-ethanol extract was not immunotoxic to mice and was able to modulate distinct patterns of the immune system in a dose-dependent manner. Copyright © 2011 John Wiley & Sons, Ltd.

  9. Regulation of the Th1 immune response : the role of IL-23 and the influence of genetic variations

    NARCIS (Netherlands)

    Wetering, Diederik van de

    2010-01-01

    Part 1: The role of IL-23 in inducing IFN-g production and in the initiation of a Th1 response. Part 2: Genetic variations in the type-1 cytokine pathway. Part 3: Treatment options for a genetic deficiency in the type-1 cytokine pathway

  10. Boswellia carterii Extract Inhibits TH1 Cytokines and Promotes TH2 Cytokines In Vitro

    OpenAIRE

    Chevrier, Marc R.; Ryan, Abigail E.; Lee, David Y.-W.; Zhongze, Ma; Wu-Yan, Zhang; Via, Charles S.

    2005-01-01

    Traditional herbal formulas used to treat inflammatory arthritis in China and India include Boswellia carterii or Boswellia serrata. They both contain boswellic acids (BAs) which have been shown to exhibit anti-inflammatory and antiarthritic properties. This study tests the hypothesis that mixtures of BAs derived from B. carterii have immunomodulatory properties. B. carterii plant resin obtained from China was prepared as an ethanol extract, and the presence of seven BAs was confirmed by colu...

  11. The imbalance of helper T lymphocytes and cytotoxic T lymphocytes in acute renal transplantation rejection

    Institute of Scientific and Technical Information of China (English)

    YAN JIANG; ZHI QIN TANG; LIN PENG; YU LIANG WANG; ZHI PING WANG

    2007-01-01

    To investigate the imbalance state of helper T lymphocytes (Th) and cytotoxic T lymphocytes (Tc) and the roles of Th1/Th2/Th3 and Tc1/Tc2 cells in renal transplantation rejection, the percentages of these cells in peripheral blood of 24 cases of renal transplantation recipients with acute rejection and the dynamic changes of the CD4/CD8 ratio were determined by flow cytometry analysis,while 30 cases of healthy individuals were set up as controls. In these healthy controls, the percentages of the Th1, Th2 and Th3 cells were (10.45±8.15)%, (5.05±4.15)% and (3.90±3.21)%,and those of Tc1 and Tc2 cells were (9.83±7.03)% and (4.51±2.17)%, respectively. However,the percentages of Th1 and Tc1 cells in peripheral blood of the stable recipients after transplantation were (7.29±5.62)% and (7.04±5.15)%, showing definite reduction, while those of Th2, Th3and Tc2 cells showed significant increase, (6.34±5.67)%, (4.94±4.14) % and ( 6.86 ±4.42) %, respectively. In case of recipients with acute rejection, the percentages of Th1 and Tc1 cells appeared to be (18.55±13.21)% and (15.84±11.72)%, also showing significant increase, but those of Th2,Th3 and Tc2 cells appeared to be reduced, (4.19±3.62)%, (3.02±2.83)% and (3.88±1.63) %, respectively. Significant differences could be detected among these three groups (P <0.05). The CD4/CD8 ratio in cases with acute rejection was higher than those of stable recipients (2.24±0.59 vs 1.95±0.45), but that of the stable recipients and healthy controls (1.98±0.31 )showed no any significant difference. From the above observation, it is evident that imbalance between Th1, Th2 and Th3 with Te1 and Tc2 cells may exist after renal transplantation and probably, the immune imbalance may be induced through the secretion of cytokines INF-γ by Th1 or Te1 cells , I1-4 by Th2 and Tc2 cells and TGF-β by Th3.

  12. Graves病发病机制中T淋巴细胞的研究进展%Research Progress of T Lymphocytes in Pathogenesis of Graves' Disease

    Institute of Scientific and Technical Information of China (English)

    马学芹

    2013-01-01

    Graves病(GD)是甲状腺功能亢进症最常见的类型,占85% ~90%,其发病机制尚未完全明了.但作为一种自身免疫性甲状腺疾病,T淋巴细胞在其发病机制中起着举足轻重的作用,Th1、Th2、Treg及Th1/Th2细胞因子失衡与其发生关系密切.近年来发现Th17及其相关因子可能在GD发病机制中起重要作用.该文就Th1、Th2、Th17及Treg与GD关系的研究进展进行综述.%Graves disease is the most common type of hyperthyroidism,accounting for 85%-90% of the total, the pathogenesis of which is not entirely clear yet. But as an autoimmune thyroid disease, T lymphocytes plays an important role in the pathogenesis. Th1 , Th2, Treg and Th1/Th2 cytokines imbalance are closely associated with the pathogenesis of Graves disease. In recent years, Th17 and its related cytokines may play an essential role in the pathogenesis of Graves disease. Here is to make a review on the relationship between Th1 ,Th2 ,Th17,Treg and Graves disease.

  13. 两种不同刺激剂对鸡淋巴细胞分泌细胞因子的影响%Effect of Two Kinds of Stimuli on Cytokines Secreted by Chicken Peripheral Blood Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    刘洪明; 王官晓; 王俊卿; 杨玉华; 郭善娜; 徐晓静

    2016-01-01

    [目的]比较不同刺激剂刀豆素A(Con A)和植物凝素(PHA)对鸡淋巴细胞分泌细胞因子的影响。[方法]首先,应用淋巴细胞分离液分离健康鸡的外周血淋巴细胞,应用2种不同的刺激剂Con A和PHA刺激48 h后收集细胞,抽提刺激培养细胞RNA,反转录。其次,应用实时定量PCR方法检测不同刺激剂对鸡淋巴细胞因子mRNA的表达。最后,用分子生物学软件对数据进行比对分析。[结果]分离到纯度和活细胞较高的鸡淋巴细胞。荧光定量PCR结果显示:Con A刺激的淋巴细胞因子表达量比PHA刺激细胞的表达量明显升高(P0.05)。[结论] Con A刺激淋巴细胞后,可以提高细胞因子的表达,刺激效果优于PHA。这些实验结果为进一步体外研究鸡淋巴细胞及其功能提供了方法。%Objective]To compare the effect of two kinds of stimuli,concanavalin A(Con A)and phytohemaggluti-nin(PHA)on cytokine secreted by chicken lymphocyte. [Methods] First,peripheral blood lymphocytes from chick-ens were separated by lymphocyte separation liquid and cultured with Con A and PHA for 48 h,respectively,then the cell RNAs were extracted and the reverse transcription was carry out. Secondly,a real time PCR was performed for detection of the RNA transcription level in the chicken lymphocytes stimulated by Con A and PHA. Finally,the effect of two kinds of stimuli on cytokines secretion was compared with molecular biology software. [Results]Chicken lym-phocytes with higher purity and a survival rate were obtained with the used method. The transcription levels of tested cy-tokines stimulated by Con A were evidently higher than that by PHA(P 0.05)except of IL-4(P < 0.01). [Conclusion]Con A can enhance the transcription levels of cytokine genes and is a be better stimulus for chicken lymphocytes than PHA. All these results provide methods for the further study of chic ken lymphocytes in vitro.

  14. N-3 fatty acids modulate Th1 and Th2 dichotomy in diabetic pregnancy and macrosomia.

    Science.gov (United States)

    Khan, Naim Akhtar; Yessoufou, Akadiri; Kim, Minji; Hichami, Aziz

    2006-06-01

    We assessed the implication of Th (helper)-cells and the modulation of the Th1/Th2 dichotomy by n-3 polyunsaturated fatty acids (PUFA) in type I diabetic pregnancy (DP) and macrosomia. Female gestant rats fed a standard diet or n-3 PUFA regimen were rendered diabetic by administration of five low doses of streptozotocin. The macrosomic (MAC) offspring were sacrificed at the age of 90 days. The mRNAs of IL-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine) were downregulated in the pancreas and spleen of diabetic pregnant rats. The levels of IL-10 mRNA, another Th2 cytokine, were unchanged in the spleen or upregulated in the pancreas of these animals. Feeding an n-3 PUFA diet to rats with DP upregulated IL-10 mRNA in the pancreas and IL-4 and IL-10 mRNA in the spleen. In MAC offspring, high expression of IL-2 and IFN-gamma mRNA, but not of Th2 cytokines, was observed. The n-3 PUFA diet diminished Th1 mRNA quantities and increased the levels of IL-4, but not of IL-10, mRNA in MAC offspring. Our study shows that DP is associated with a decreased Th1 phenotype and IL-4 mRNA expression in the pancreas and spleen, and an n-3 PUFA diet upregulates Th2 profile. In MAC offspring, the Th1 phenotype is upregulated and an n-3 PUFA diet downregulates this phenomenon.

  15. Differences in APOBEC3G expression in CD4+ T helper lymphocyte subtypes modulate HIV-1 infectivity.

    Directory of Open Access Journals (Sweden)

    Michael L Vetter

    2009-02-01

    Full Text Available The cytidine deaminases APOBEC3G and APOBEC3F exert anti-HIV-1 activity that is countered by the HIV-1 vif protein. Based on potential transcription factor binding sites in their putative promoters, we hypothesized that expression of APOBEC3G and APOBEC3F would vary with T helper lymphocyte differentiation. Naive CD4+ T lymphocytes were differentiated to T helper type 1 (Th1 and 2 (Th2 effector cells by expression of transcription factors Tbet and GATA3, respectively, as well as by cytokine polarization. APOBEC3G and APOBEC3F RNA levels, and APOBEC3G protein levels, were higher in Th1 than in Th2 cells. T cell receptor stimulation further increased APOBEC3G and APOBEC3F expression in Tbet- and control-transduced, but not in GATA3-transduced, cells. Neutralizing anti-interferon-gamma antibodies reduced both basal and T cell receptor-stimulated APOBEC3G and APOBEC3F expression in Tbet- and control-transduced cells. HIV-1 produced from Th1 cells had more virion APOBEC3G, and decreased infectivity, compared to virions produced from Th2 cells. These differences between Th1- and Th2-produced virions were greater for viruses lacking functional vif, but also seen with vif-positive viruses. Over-expression of APOBEC3G in Th2 cells decreased the infectivity of virions produced from Th2 cells, and reduction of APOBEC3G in Th1 cells increased infectivity of virions produced from Th1 cells, consistent with a causal role for APOBEC3G in the infectivity difference. These results indicate that APOBEC3G and APOBEC3F levels vary physiologically during CD4+ T lymphocyte differentiation, that interferon-gamma contributes to this modulation, and that this physiological regulation can cause changes in infectivity of progeny virions, even in the presence of HIV-1 vif.

  16. IL-33 alleviates DSS-induced chronic colitis in C57BL/6 mice colon lamina propria by suppressing Th17 cell response as well as Th1 cell response.

    Science.gov (United States)

    Zhu, Junfeng; Wang, Yuanyuan; Yang, Fangli; Sang, Lixuan; Zhai, Jingbo; Li, Shengjun; Li, Yan; Wang, Danan; Lu, Changlong; Sun, Xun

    2015-12-01

    Interleukin (IL)-33, a member of the IL-1 cytokine family, is associated with autoimmune diseases including inflammatory bowel diseases (IBD). A few studies on animal models have shown that IL-33 can suppress Th1 cell response and improve Th2 cell response in mesenteric lymph nodes (MLN) and sera. However, there is little data published about the effect of IL-33 on Th17 cell in and Th1/Th2 cell in colon lamina propria. The aim of this study was to investigate the effect of IL-33 on Th17 cell in colon lamina propria of mice with dextran sulfate sodium (DSS) induced chronic colitis. We studied the influence of IL-33 on colonic tissue injury and clinical symptoms of colitis. The T cell subsets were measured by flow cytometry and the production of cytokines secreted by lamina propria lymphocytes (LPL) was measured by Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative real-time PCR. We have found that rIL-33 treatment led to a significant alleviation of DSS induced chronic colitis as evidenced by 1) alleviation of weight loss, DAI, macroscopic changes and histological score; 2) down-regulating the rates and absolute cell numbers of Th17 and Th1 cell in LPL; 3) inducing secretion of lower levels of IFN-γ and IL-17A. It is therefore concluded that IL-33 may play a therapeutic role in DSS-induced chronic colitis in mice by suppressing Th17 response and switching Th1 to Th2 response.

  17. Characterization of T cell receptors of Th1 cells infiltrating inflamed skin of a novel murine model of palladium-induced metal allergy.

    Directory of Open Access Journals (Sweden)

    Hiroshi Kobayashi

    Full Text Available Metal allergy is categorized as a delayed-type hypersensitivity reaction, and is characterized by the recruitment of lymphocytes into sites of allergic inflammation. Because of the unavailability of suitable animal models for metal allergy, the role of T cells in the pathogenesis of metal allergy has not been explored. Thus, we developed a novel mouse model for metal allergy associated with infiltration of T cells by multiple injections of palladium (Pd plus lipopolysaccharide into the footpad. Using this model, we characterized footpad-infiltrating T cells in terms of phenotypic markers, T cell receptor (TCR repertoires and cytokine expression. CD3+ CD4+ T cells accumulated in the allergic footpads 7 days after Pd challenge. The expression levels of CD25, interleukin-2, interferon-γ and tumor necrosis factor, but not interleukin-4 and interleukin-5, increased in the footpads after challenge, suggesting CD4+ T helper 1 (Th1 cells locally expanded in response to Pd. Infiltrated T cells in the footpads frequently expressed AV18-1 and BV8-2 T cell receptor (TCR chains compared with T cells in the lymph nodes and exhibited oligoclonality. T-cell clones identified from Pd-allergic mouse footpads shared identical CDR3 sequences containing AV18-1 and BV8-2. These results suggest that TCR AV18-1 and BV8-2 play dominant and critical parts in the antigen specificity of Pd-specific Th1 cells.

  18. Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs in vitro

    Directory of Open Access Journals (Sweden)

    Xia Yang

    2012-01-01

    Full Text Available Thymosin alpha 1 (Tα1 has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs from gastric carcinoma patients (N = 35 and healthy donors (N = 22. We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05. Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

  19. Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xia [Institute of Immunology,Third Military Medical University, Chongqing (China); Qian, Feng [Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing (China); He, Hai-Yang; Liu, Kai-Jun [Institute of Immunology,Third Military Medical University, Chongqing (China); Lan, Yuan-Zhi [Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing (China); Ni, Bing; Tian, Yi; Fu, Xiao-Lan; Zhang, Ji; Shen, Zi-Gang; Li, Jian; Yin, Yi; Li, Jin-Tao; Wu, Yu-Zhang [Institute of Immunology,Third Military Medical University, Chongqing (China)

    2011-12-02

    Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4{sup +} and CD8{sup +} T cells, especially the CD4{sup +}CD25{sup +}Foxp3{sup +} Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

  20. Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro.

    Science.gov (United States)

    Yang, Xia; Qian, Feng; He, Hai-Yang; Liu, Kai-Jun; Lan, Yuan-Zhi; Ni, Bing; Tian, Yi; Fu, Xiao-Lan; Zhang, Ji; Shen, Zi-Gang; Li, Jian; Yin, Yi; Li, Jin-Tao; Wu, Yu-Zhang

    2012-01-01

    Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

  1. Functional and pathogenic differences of Th1 and Th17 cells in experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Helena S Domingues

    Full Text Available BACKGROUND: There is consensus that experimental autoimmune encephalomyelitis (EAE can be mediated by myelin specific T cells of Th1 as well as of Th17 phenotype, but the contribution of either subset to the pathogenic process has remained controversial. In this report, we compare functional differences and pathogenic potential of "monoclonal" T cell lines that recognize myelin oligodendrocyte glycoprotein (MOG with the same transgenic TCR but are distinguished by an IFN-γ producing Th1-like and IL-17 producing Th17-like cytokine signature. METHODS AND FINDINGS: CD4+ T cell lines were derived from the transgenic mouse strain 2D2, which expresses a TCR recognizing MOG peptide 35-55 in the context of I-A(b. Adoptive transfer of Th1 cells into lymphopenic (Rag2⁻/⁻ recipients, predominantly induced "classic" paralytic EAE, whereas Th17 cells mediated "atypical" ataxic EAE in approximately 50% of the recipient animals. Combination of Th1 and Th17 cells potentiated the encephalitogenicity inducing classical EAE exclusively. Th1 and Th17 mediated EAE lesions differed in their composition but not in their localization within the CNS. While Th1 lesions contained IFN-γ, but no IL-17 producing T cells, the T cells in Th17 lesions showed plasticity, substantially converting to IFN-γ producing Th1-like cells. Th1 and Th17 cells differed drastically by their lytic potential. Th1 but not Th17 cells lysed autoantigen presenting astrocytes and fibroblasts in vitro in a contact-dependent manner. In contrast, Th17 cells acquired cytotoxic potential only after antigenic stimulation and conversion to IFN-γ producing Th1 phenotype. CONCLUSIONS: Our data demonstrate that both Th1 and Th17 lineages possess the ability to induce CNS autoimmunity but can function with complementary as well as differential pathogenic mechanisms. We propose that Th17-like cells producing IL-17 are required for the generation of atypical EAE whereas IFN-γ producing Th1 cells induce

  2. Oral supplementation of diabetic mice with propolis restores the proliferation capacity and chemotaxis of B and T lymphocytes towards CCL21 and CXCL12 by modulating the lipid profile, the pro-inflammatory cytokine levels and oxidative stress.

    Science.gov (United States)

    Al Ghamdi, Ahmad A; Badr, Gamal; Hozzein, Wael N; Allam, Ahmed; Al-Waili, Noori S; Al-Wadaan, Mohammed A; Garraud, Olivier

    2015-09-15

    Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the selective destruction of pancreatic β cells, followed by hyperglycemia, oxidative stress and the subsequent extensive impairment of immune cell functions, a phenomenon responsible for the development of chronic diabetic complications. Propolis, a natural bee product that is extensively used in foods and beverages, significantly benefits human health. Specifically, propolis exerts antioxidant, anti-inflammatory and analgesic effects that may improve diabetic complications. To further elucidate the potential benefits of propolis, the present study investigated the effect of dietary supplementation with propolis on the plasma cytokine profiles, free radical levels, lipid profile and lymphocyte proliferation and chemotaxis in a streptozotocin (STZ)-induced type I diabetic mouse model. Thirty male mice were equally distributed into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice supplemented daily with an ethanol-soluble derivative of propolis (100 mg/kg body weight) for 1 month. First, the induction of diabetes in mice was associated with hyperglycemia and significant decreases in the insulin level and the lymphocyte count. In this context, diabetic mice exhibited severe diabetic complications, as demonstrated by a significant decrease in the levels of IL-2, IL-4 and IL-7, prolonged elevation of the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and reactive oxygen species (ROS) and altered lipid profiles compared with control non-diabetic mice. Moreover, antigen stimulation of B and T lymphocytes markedly reduced the proliferative capacity and chemotaxis of these cells towards CCL21 and CXCL12 in diabetic mice compared with control mice. Interestingly, compared with diabetes induction alone, treatment of diabetic mice with propolis significantly restored the plasma cytokine and ROS levels and the lipid profile to

  3. The TLR4 Agonist Vaccine Adjuvant, GLA-SE, Requires Canonical and Atypical Mechanisms of Action for TH1 Induction.

    Science.gov (United States)

    Dubois Cauwelaert, Natasha; Desbien, Anthony L; Hudson, Thomas E; Pine, Samuel O; Reed, Steven G; Coler, Rhea N; Orr, Mark T

    2016-01-01

    The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) promotes strong TH1 and balanced IgG1/IgG2 responses to protein vaccine antigens. This enhanced immunity is sufficient to provide protection against many diseases including tuberculosis and leishmaniasis. To better characterize the adjuvant action it is important to understand how the different cytokines and transcription factors contribute to the initiation of immunity. In the present study using T-bet-/- and IL-12-/- mice and a blocking anti-IFNαR1 monoclonal antibody, we define mechanisms of adjuvant activity of GLA-SE. In accordance with previous studies of TLR4 agonist based adjuvants, we found that TH1 induction via GLA-SE was completely dependent upon T-bet, a key transcription factor for IFNγ production and TH1 differentiation. Consistent with this, deficiency of IL-12, a cytokine canonical to TH1 induction, ablated TH1 induction via GLA-SE. Finally we demonstrate that the innate immune response to GLA-SE, including rapid IFNγ production by memory CD8+ T cells and NK cells, was contingent on type I interferon, a cytokine group whose association with TH1 induction is contextual, and that they contributed to the adjuvant activity of GLA-SE.

  4. The TLR4 Agonist Vaccine Adjuvant, GLA-SE, Requires Canonical and Atypical Mechanisms of Action for TH1 Induction.

    Directory of Open Access Journals (Sweden)

    Natasha Dubois Cauwelaert

    Full Text Available The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE promotes strong TH1 and balanced IgG1/IgG2 responses to protein vaccine antigens. This enhanced immunity is sufficient to provide protection against many diseases including tuberculosis and leishmaniasis. To better characterize the adjuvant action it is important to understand how the different cytokines and transcription factors contribute to the initiation of immunity. In the present study using T-bet-/- and IL-12-/- mice and a blocking anti-IFNαR1 monoclonal antibody, we define mechanisms of adjuvant activity of GLA-SE. In accordance with previous studies of TLR4 agonist based adjuvants, we found that TH1 induction via GLA-SE was completely dependent upon T-bet, a key transcription factor for IFNγ production and TH1 differentiation. Consistent with this, deficiency of IL-12, a cytokine canonical to TH1 induction, ablated TH1 induction via GLA-SE. Finally we demonstrate that the innate immune response to GLA-SE, including rapid IFNγ production by memory CD8+ T cells and NK cells, was contingent on type I interferon, a cytokine group whose association with TH1 induction is contextual, and that they contributed to the adjuvant activity of GLA-SE.

  5. Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Morzadec, Claudie; Macoch, Mélinda; Robineau, Marc; Sparfel, Lydie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2012-08-01

    Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with activation of

  6. Rat acute GvHD is Th1-driven and characterized by predominant donor CD4(+) T cell infiltration of skin and gut.

    Science.gov (United States)

    Boieri, Margherita; Shah, Pranali; Jalapothu, Dasaradha; Zaitseva, Olena; Walter, Lutz; Rolstad, Bent; Naper, Christian; Dressel, Ralf; Inngjerdingen, Marit

    2017-02-23

    Acute graft-versus-host disease (aGvHD) remains a significant hurdle to successful treatment of many hematological disorders. The disease is caused by infiltration of allo-activated donor T cells primarily into the gastrointestinal tract and skin. While cytotoxic T cells mediate direct cellular damage, T helper (Th) cells differentially secrete immunoregulatory cytokines. Acute GvHD is thought to be primarily initiated by Th1 cells but a consensus is still lacking regarding the role of Th2 and Th17 cells. The aim of this study was to determine the contribution of distinct T cell subsets to aGvHD in the rat. Acute GvHD was induced by transplanting irradiated rats with T-cell depleted MHC-mismatched bone marrow, followed two weeks later by donor lymphocyte infusion. Near complete donor T cell chimerism was achieved in the blood and lymphatic tissues, in contrast to mixed chimerism in the skin and gut. Skin and gut donor T cells were predominantly CD4(+), in contrast to T cells in blood and lymphatic tissues. Genes associated with Th1 cells were up-regulated in gut, liver, lung, and skin tissues affected by aGvHD. Increased serum levels of CXCL10 and IL-18 preceded symptoms of aGvHD, accompanied by increased responsiveness to CXCL10 by blood CD4(+) T cells. No changes in expression of Th2- or Th17-associated genes were observed, indicating that aGvHD in this rat model is mainly Th1-driven. The rat model of aGvHD could be instrumental for further investigations of donor T cell subsets in the skin and gut, and for exploring therapeutic options to ameliorate symptoms of aGvHD.

  7. Electro-acupuncture at Acupoint ST36 Ameliorates Inflammation and Regulates Th1/Th2 Balance in Delayed-Type Hypersensitivity.

    Science.gov (United States)

    Wang, Zhigang; Chen, Tao; Long, Man; Chen, Longyun; Wang, Lei; Yin, Nina; Chen, Zebin

    2017-04-01

    Increasing evidence indicates anti-allergic and anti-inflammatory effects of electro-acupuncture (EA) therapy. However, its underlying mechanism on delayed-type hypersensitivity (DTH), a classic allergic inflammatory disease, still remains unclear. In this study, we aimed to explore the immunomodulatory mechanism of EA intervention in a mouse model of ovalbumin (OVA)-induced DTH. Mice were randomly divided into four groups: Control, OVA-DTH, DTH + EA, DTH + Sham. "Zusanli" acupoint (ST36) was used for DTH + EA, whereas a non-acupoint (localized 5 mm below the "Zusanli" acupoint) was selected for DTH + Sham. Footpad thickness was checked, and the infiltration of inflammatory cells was estimated by hematoxylin and eosin staining. Levels of IgG and IgE in serum of different groups and inflammatory cytokines in the supernatants from homogenized footpads, including IFN-γ, TNF-α, IL-4, and IL-5, were determined by ELISA. Cell proliferation of spleen lymphocytes was assayed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT). The frequency of CD4(+)IFN-γ(+) and CD4(+)IL-4(+) T cells was analyzed with flow cytometry. In addition, the mRNA and protein expression of T-bet and GATA-3 were evaluated by real-time PCR and Western blotting, respectively. Our data showed EA treatment at acupoint ST36 relieved the pathological progression of DTH responses via reduction in footpad swelling, infiltration of inflammatory cells, levels of IgG and IgE as well as decreased production of IFN-γ and TNF-α in homogenized footpad tissue. Moreover, detailed studies were performed revealing that EA attenuated the percentage of CD4(+)IFN-γ(+) T cells and prevented Th cells differentiation into Th1 cells, and this results from inhibiting secretion of IFN-γ and suppressing expression of T-bet, an IFN-γ transcription factor. The results indicated that EA treatment improved Th1-mediated allergic skin inflammation via restoring Th1/Th2 balance by curbing Th1

  8. Cytokine Gene Expression in CD4 Positive Cells of the Japanese Pufferfish, Takifugu rubripes.

    Directory of Open Access Journals (Sweden)

    Tomoya Kono

    Full Text Available CD4(+ T (Th cells are a central component of the adaptive immune response and are divided into distinct sets based on their specific cytokine production pattern. Several reports have suggested that fish possess Th subset activity similar to that of mammals. The aim of the present study was to isolate CD4(+ T cells from the blood of Japanese pufferfish, Fugu rubripes, and to characterize their cytokine expression profile. We produced a specific antibody against Fugu CD4 and performed cell sorting with the magnetic activated cell sorting system. Sorted Fugu CD4(+ cells were characterized by morphology and expression analysis of cell marker genes. Fugu CD4(+ cells expressed T-cell marker genes but not macrophage or B-cell marker genes. In addition, peripheral blood lymphocytes were stimulated with lipopolysaccharide (LPS, polycytidylic acid (polyI:C, concanavalin A (ConA prior to sorting, and then Multiplex RT-PCR was used to examine the expression of Th cytokines by the stimulated Fugu CD4(+ cells. LPS and polyI:C stimulation upregulated the expression of Th1, Th17 and Treg cytokines and downregulated the expression of Th2 cytokines. ConA stimulation upregulated the expression of all Th cytokines. These results suggest that fish exhibit the same upregulation of Th-specific cytokine expression as in mammals.

  9. T lymphocyte subset imbalances in patients contribute to ankylosing spondylitis

    Science.gov (United States)

    WANG, CHENGGONG; LIAO, QIANDE; HU, YIHE; ZHONG, DA

    2015-01-01

    Ankylosing spondylitis is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the spine and the sacroiliac joints. To date, the disease etiology remains unclear. In the present study, the correlation of T lymphocyte subset changes with the progression of ankylosing spondylitis was investigated. A total of 55 patients with ankylosing spondylitis (22 severe and 23 mild cases) and 20 healthy individuals were selected. Firstly, the punctured cells in the lesions and the serum were collected, and the lymphocytes and the peripheral blood mononuclear cells were prepared. Secondly, quantitative PCR, ELISA and flow cytometry analyses were carried out to detect the levels of a series of immunoglobulins, complements, helper T cells, cytotoxic T cells, regulatory cells and cytokines. The expression levels of α-globulin, γ-globulin, immunoglobulin (Ig)G, IgA, IgM, serum complement C3, and complement C4 were found to be significantly increased in ankylosing spondylitis patients. In addition, the percentage of Th1 and Th17 cells was found to be significantly higher in the ankylosing spondylitis groups (mild and severe) compared with the healthy individuals. As a result, the Th1/Th2 and Th17/Treg ratios were significantly higher in patients with ankylosing spondylitis. In addition, T lymphocyte subset ratio imbalances contributed to an increased expression of immune mediators, including interferon (IFN)-γ and interleukin (IL)-17A. The mRNA and protein expression levels of IFN-γ and IL-17A were found to be higher in the ankylosing spondylitis groups compared with the control group. The present study provided further evidence on the function and underlying mechanism of T lymphocyte subsets, which may be useful in the diagnosis and treatment of ankylosing spondylitis. PMID:25452811

  10. T lymphocyte subset imbalances in patients contribute to ankylosing spondylitis.

    Science.gov (United States)

    Wang, Chenggong; Liao, Qiande; Hu, Yihe; Zhong, DA

    2015-01-01

    Ankylosing spondylitis is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the spine and the sacroiliac joints. To date, the disease etiology remains unclear. In the present study, the correlation of T lymphocyte subset changes with the progression of ankylosing spondylitis was investigated. A total of 55 patients with ankylosing spondylitis (22 severe and 23 mild cases) and 20 healthy individuals were selected. Firstly, the punctured cells in the lesions and the serum were collected, and the lymphocytes and the peripheral blood mononuclear cells were prepared. Secondly, quantitative PCR, ELISA and flow cytometry analyses were carried out to detect the levels of a series of immunoglobulins, complements, helper T cells, cytotoxic T cells, regulatory cells and cytokines. The expression levels of α-globulin, γ-globulin, immunoglobulin (Ig)G, IgA, IgM, serum complement C3, and complement C4 were found to be significantly increased in ankylosing spondylitis patients. In addition, the percentage of Th1 and Th17 cells was found to be significantly higher in the ankylosing spondylitis groups (mild and severe) compared with the healthy individuals. As a result, the Th1/Th2 and Th17/Treg ratios were significantly higher in patients with ankylosing spondylitis. In addition, T lymphocyte subset ratio imbalances contributed to an increased expression of immune mediators, including interferon (IFN)-γ and interleukin (IL)-17A. The mRNA and protein expression levels of IFN-γ and IL-17A were found to be higher in the ankylosing spondylitis groups compared with the control group. The present study provided further evidence on the function and underlying mechanism of T lymphocyte subsets, which may be useful in the diagnosis and treatment of ankylosing spondylitis.

  11. BOB.1/OBF.1 controls the balance of TH1 and TH2 immune responses.

    Science.gov (United States)

    Brunner, Cornelia; Sindrilaru, Anca; Girkontaite, Irute; Fischer, Klaus-Dieter; Sunderkötter, Cord; Wirth, Thomas

    2007-07-11

    BOB.1/OBF.1 is a transcriptional coactivator essential at several stages of B-cell development. In T cells, BOB.1/OBF.1 expression is inducible by co-stimulation. However, a defined role of BOB.1/OBF.1 for T-cell function had not been discovered so far. Here, we show that BOB.1/OBF.1 is critical for T helper cell function. BOB.1/OBF.1(-/-) mice showed imbalanced immune responses, resulting in increased susceptibility to Leishmania major infection. Functional analyses revealed specific defects in TH1 and TH2 cells. Whereas expression levels of TH1 cytokines were reduced, the secretion of TH2 cytokines was increased. BOB.1/OBF.1 directly contributes to the IFNgamma and IL2 promoter activities. In contrast, increased TH2 cytokine production is controlled indirectly, probably via the transcription factor PU.1, the expression of which is regulated by BOB.1/OBF.1. Thus, BOB.1/OBF.1 regulates the balance of TH1 versus TH2 mediated immunity.

  12. Inflammatory cytokine regulation by LPS and lymphoid cells in human gamma-irradiated monocytes/macrophages; Regulation des cytokines de l`inflammation en presence de LPS ou de lymphocytes dans les monocytes/macrophages humains irradies

    Energy Technology Data Exchange (ETDEWEB)

    Pons, I.; Gras, G.; Dormont, D. [Centre de Recherches du Service de Sante des Armees, La Tronche, 38 - Grenoble (France)]|[Centre de Recherches du Service de Sante des Armees - Centre d`Etudes Nucleaires de Fontenay-aux-Roses, 92 (France)]|[Paris-5 Univ., 75 (France)

    1997-12-31

    We have investigated the inflammatory cytokine regulation after ionizing radiation of monocytes/macrophages. We have not evidenced any significant induction of tumour necrosis factor-{alpha}(TNF{alpha}) after irradiation alone. For one donor only out of eight, interleukin-1{beta}(IL-l{beta}) gene expression was affected by {gamma}-irradiation, with a 2-3-fold increase in level, while for two other donors, interleukin-6 (IL-6) mRNA expression was 5-14 fold increased. For one of the eight donors tested, monocytes/macrophages responded to 10 Gy {gamma}-rays by releasing inflammatory cytokines. In the presence of LPS, a significant increase of IL-1{beta} mRNA expression was detected in 10 Gy {gamma}-irradiated cells treated with 1 {mu}g/ml LPS. In most cases, combination of LPS treatment and 10 Gy irradiation down-regulated cytokine secretion except for a TNF{alpha} induction at 6 h post-irradiation. In the presence of lymphoid cells, IL-6 mRNA level was increased in irradiated cells at 24 h. Increases of IL-1{beta} and IL-6 releases were detected at 24 h post-irradiation too. (authors)

  13. The Role of Neutrophils in the Induction of Specific Th1 and Th17 during Vaccination against Tuberculosis

    Science.gov (United States)

    Trentini, Monalisa M.; de Oliveira, Fábio M.; Kipnis, André; Junqueira-Kipnis, Ana P.

    2016-01-01

    Mycobacterium tuberculosis causes tuberculosis (TB), a disease that killed more than 1.5 million people worldwide in 2014, and the Bacillus Calmette Guérin (BCG) vaccine is the only currently available vaccine against TB. However, it does not protect adults. Th1 and Th17 cells are crucial for TB control, as well as the neutrophils that are directly involved in DC trafficking to the draining lymph nodes and the activation of T lymphocytes during infection. Although several studies have shown the importance of neutrophils during M. tuberculosis infection, none have shown its role in the development of a specific response to a vaccine. The vaccine mc2-CMX was shown to protect mice against M. tuberculosis challenge, mainly due to specific Th1 and Th17 cells. This study evaluated the importance of neutrophils in the generation of the Th1- and Th17-specific responses elicited by this vaccine. The vaccine injection induced a neutrophil rich lesion with a necrotic central area. The IL-17 KO mice did not generate vaccine-specific Th1 cells. The vaccinated IL-22 KO mice exhibited Th1- and Th17-specific responses. Neutrophil depletion during vaccination abrogated the induction of Th1-specific responses and prohibited the bacterial load reduction observed in the vaccinated animals. The results show, for the first time, the role of neutrophils in the generation of specific Th1 and Th17 cells in response to a tuberculosis vaccine. PMID:27375607

  14. Circulating levels of Th1 and Th2 chemokines in patients with ankylosing spondylitis.

    Science.gov (United States)

    Wang, Jianing; Zhao, Qi; Wang, Gaoya; Yang, Chunshu; Xu, Yong; Li, Yujia; Yang, Pingting

    2016-05-01

    Although chemokines are critical elements for the selective attraction and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning T helper (Th) 1 or Th2 chemokines in ankylosing spondylitis (AS). This study was designed to determine whether serum levels of chemokines that are preferentially chemotactic for Th1 (IFN-gamma-inducible protein-10, IP-10/CXCL10) and Th2 (thymus and activation regulated chemokine, TARC/CCL17) and (macrophage derived chemokine, MDC/CCL22) cells were elevated and whether they correlated with the clinical features in patients with AS. Forty-two patients with axial AS and 25 healthy controls were enrolled into the study. Serum levels of chemokines (IP-10, TARC and MDC) and cytokines (IFN-γ, TNF-α and IL-4) were examined using ELISA. The disease activity was evaluated by Ankylosing Spondylitis Disease Activity Score (ASDAS). Serum levels of IgG, IgA, IgM, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured. Serum chemokine levels of IP-10, TARC and MDC were significantly higher in patients with AS than those in healthy controls. Serum cytokine levels of IFN-γ, TNF-α were also significantly increased, but the levels of IL-4 were not. Furthermore, IP-10 levels in AS patients correlated with ESP, CRP and ASDAS, while the levels of TARC and MDC did not correlate with these clinic indexes. Correlation analysis between the levels of chemokines and cytokines revealed a positive correlation between IP-10 and TNF-α. The levels of both Th1 and Th2 chemokines decreased under blockade of TNF-α. Our results suggest that both a Th1 chemoattractant IP-10 and Th2 chemoattractants, TARC and MDC, cooperatively play a role in the development of AS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade.

    Science.gov (United States)

    Stojanov, Silvia; Lapidus, Sivia; Chitkara, Puja; Feder, Henry; Salazar, Juan C; Fleisher, Thomas A; Brown, Margaret R; Edwards, Kathryn M; Ward, Michael M; Colbert, Robert A; Sun, Hong-Wei; Wood, Geryl M; Barham, Beverly K; Jones, Anne; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; Athreya, Balu; Barron, Karyl S; Kastner, Daniel L

    2011-04-26

    The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever disease in children. However, the pathogenesis is unknown. Using a systems biology approach we analyzed blood samples from PFAPA patients whose genetic testing excluded hereditary periodic fevers (HPFs), and from healthy children and pediatric HPF patients. Gene expression profiling could clearly distinguish PFAPA flares from asymptomatic intervals, HPF flares, and healthy controls. During PFAPA attacks, complement (C1QB, C2, SERPING1), IL-1-related (IL-1B, IL-1RN, CASP1, IL18RAP), and IFN-induced (AIM2, IP-10/CXCL10) genes were significantly overexpressed, but T cell-associated transcripts (CD3, CD8B) were down-regulated. On the protein level, PFAPA flares were accompanied by significantly increased serum levels of chemokines for activated T lymphocytes (IP-10/CXCL10, MIG/CXCL9), G-CSF, and proinflammatory cytokines (IL-18, IL-6). PFAPA flares also manifested a relative lymphopenia. Activated CD4(+)/CD25(+) T-lymphocyte counts correlated negatively with serum concentrations of IP-10/CXCL10, whereas CD4(+)/HLA-DR(+) T lymphocyte counts correlated positively with serum concentrations of the counterregulatory IL-1 receptor antagonist. Based on the evidence for IL-1β activation in PFAPA flares, we treated five PFAPA patients with a recombinant IL-1 receptor antagonist. All patients showed a prompt clinical and IP-10/CXCL10 response. Our data suggest an environmentally triggered activation of complement and IL-1β/-18 during PFAPA flares, with induction of Th1-chemokines and subsequent retention of activated T cells in peripheral tissues. IL-1 inhibition may thus be beneficial for treatment of PFAPA attacks, with IP-10/CXCL10 serving as a potential biomarker.

  16. Cytokine responses in acute and persistent human parvovirus B19 infection

    DEFF Research Database (Denmark)

    Isa, A; Lundqvist, A; Lindblom, A

    2007-01-01

    The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads...

  17. TNF superfamily cytokines in the promotion of Th9 differentiation and immunopathology.

    Science.gov (United States)

    Meylan, Françoise; Siegel, Richard M

    2017-01-01

    The tumor necrosis factor (TNF) receptors and their corresponding cytokine ligands have been implicated in many aspects of the biology of immune functions. TNF receptors have key roles during various stages of T cell homeostasis. Many of them can co-stimulate lymphocyte proliferation and cytokine production. Additionally, several TNF cytokines can regulate T cell differentiation, including promoting Th1, Th2, Th17, and more recently the newly described Th9 subset. Four TNF family cytokines have been identified as regulators for IL-9 production by T cells. OX40L, TL1A, and GITRL can promote Th9 formation but can also divert iTreg into Th9, while 4-1BBL seems to inhibit IL-9 production from iTreg and has not been studied for its ability to promote Th9 generation. Regulation of IL-9 production by TNF family cytokines has repercussions in vivo, including enhancement of anti-tumor immunity and immunopathology in allergic lung and ocular inflammation. Regulating T cell production of IL-9 through blockade or agonism of TNF family cytokine receptors may be a therapeutic strategy for autoimmune and allergic diseases and in tumor.

  18. Intratumoral injection of Propionibacterium acnes suppresses malignant melanoma by enhancing Th1 immune responses.

    Directory of Open Access Journals (Sweden)

    Kenshiro Tsuda

    Full Text Available Malignant melanoma (MM is an aggressive cutaneous malignancy associated with poor prognosis; many putatively therapeutic agents have been administered, but with mostly unsuccessful results. Propionibacterium acnes (P. acnes is an aerotolerant anaerobic gram-positive bacteria that causes acne and inflammation. After being engulfed and processed by phagocytes, P. acnes induces a strong Th1-type cytokine immune response by producing cytokines such as IL-12, IFN-γ and TNF-α. The characteristic Th2-mediated allergic response can be counteracted by Th1 cytokines induced by P. acnes injection. This inflammatory response induced by P. acnes has been suggested to have antitumor activity, but its effect on MM has not been fully evaluated.We analyzed the anti-tumor activity of P. acnes vaccination in a mouse model of MM. Intratumoral administration of P. acnes successfully protected the host against melanoma progression in vivo by inducing both cutaneous and systemic Th1 type cytokine expression, including TNF-α and IFN-γ, which are associated with subcutaneous granuloma formation. P. acnes-treated tumor lesions were infiltrated with TNF-α and IFN-γ positive T cells. In the spleen, TNF-α as well as IFN-γ producing CD8(+T cells were increased, and interestingly, the number of monocytes was also increased following P. acnes administration. These observations suggest that P. acnes vaccination induces both systemic and local antitumor responses. In conclusion, this study shows that P. acnes vaccination may be a potent therapeutic alternative in MM.

  19. Th1 stimulatory proteins of Leishmania donovani: comparative cellular and protective responses of rTriose phosphate isomerase, rProtein disulfide isomerase and rElongation factor-2 in combination with rHSP70 against visceral leishmaniasis.

    Science.gov (United States)

    Jaiswal, Anil Kumar; Khare, Prashant; Joshi, Sumit; Kushawaha, Pramod Kumar; Sundar, Shyam; Dube, Anuradha

    2014-01-01

    In visceral leishmaniasis, the recovery from the disease is always associated with the generation of Th1-type of cellular responses. Based on this, we have previously identified several Th1-stimulatory proteins of Leishmania donovani -triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and elongation factor-2 (EL-2) etc. including heat shock protein 70 (HSP70) which induced Th1-type of cellular responses in both cured Leishmania patients/hamsters. Since, HSPs, being the logical targets for vaccines aimed at augmenting cellular immunity and can be early targets in the immune response against intracellular pathogens; they could be exploited as vaccine/adjuvant to induce long-term immunity more effectively. Therefore, in this study, we checked whether HSP70 can further enhance the immunogenicity and protective responses of the above said Th1-stimulatory proteins. Since, in most of the studies, immunogenicity of HSP70 of L. donovani was assessed in native condition, herein we generated recombinant HSP70 and tested its potential to stimulate immune responses in lymphocytes of cured Leishmania infected hamsters as well as in the peripheral blood mononuclear cells (PBMCs) of cured patients of VL either individually or in combination with above mentioned recombinant proteins. rLdHSP70 alone elicited strong cellular responses along with remarkable up-regulation of IFN-γ and IL-12 cytokines and extremely lower level of IL-4 and IL-10. Among the various combinations, rLdHSP70 + rLdPDI emerged as superior one augmenting improved cellular responses followed by rLdHSP70 + rLdEL-2. These combinations were further evaluated for its protective potential wherein rLdHSP70 + rLdPDI again conferred utmost protection (∼80%) followed by rLdHSP70 + rLdEL-2 (∼75%) and generated a strong cellular immune response with significant increase in the levels of iNOS transcript as well as IFN-γ and IL-12 cytokines which was further supported by the high level of IgG2 antibody

  20. Dinamic changes of pro-inflammatory cytokines, adhesion molecules and lymphocytes activation markers as early indicators of diseases severity in patients with Dengue

    Directory of Open Access Journals (Sweden)

    Silvana Vielma

    2014-09-01

    Full Text Available Several immunopathogenic mechanisms have been proposed to explain the massive increase of vascular permeability observed in the severe forms of infection by Dengue Virus (DENV. Our aim was to determine the kinetic changes of inflammatory mediators (IL-8, TNF- α, soluble early lymphocyte activation markers (sIL-2R, sTNF-Rp75 and soluble fractions of cell adhesion molecules (sICAM-1 and sVCAM-1 as indicators for early recognition of disease severity in patients with laboratory-confirmed dengue. Twenty patients classified as Dengue±Warning Signs (D±WS and thirty patients with Severe Dengue (SD were included in the study. Serums of apparently healthy individuals were included as controls. Compared with normal subjects, D±WS cases did not show significant differences in the levels of IL-8 or TNF-α during the acute nor in the critical stages of the disease; however, in D±WS cases levels of sICAM-1 and sVCAM-1 were higher than controls during both phases; in contrast, significant increase of sTNF-p75 and sIL2R levels were observed during the critical phase of the disease. Compared with both dengue patients and controls, patients with SD showed significant rise in the levels of IL-8 and TNF-α during the critical phase of the disease and a significant increase in adhesion molecules were detected in both phases, but the highest levels of sVCAM-1 and sIL-2R were observed only during the acute stage of the disease. In conclusion, sIL-2R and sVCAM-1, as early markers of lymphocyte and endothelial activation, would serves as indicators of severity during the acute phase of dengue infection.

  1. Regulation of Th1/Th2 cells in asthma development: a mathematical model.

    Science.gov (United States)

    Kim, Yangjin; Lee, Seongwon; Kim, You-Sun; Lawler, Sean; Gho, Yong Song; Kim, Yoon-Keun; Hwang, Hyung Ju

    2013-08-01

    Airway exposure levels of lipopolysaccharide (LPS) determine type I versus type II helper T cell induced experimental asthma. While high LPS levels induce Th1-dominant responses, low LPS levels derive Th2 cell induced asthma. The present paper develops a mathematical model of asthma development which focuses on the relative balance of Th1 and Th2 cell induced asthma. In the present work we represent the complex network of interactions between cells and molecules by a mathematical model. The model describes the behaviors of cells (Th0, Th1, Th2 and macrophages) and regulatory molecules (IFN- γ, IL-4, IL-12, TNF-α) in response to high, intermediate, and low levels of LPS. The simulations show how variations in the levels of injected LPS affect the development of Th1 or Th2 cell responses through differential cytokine induction. The model also predicts the coexistence of these two types of response under certain biochemical and biomechanical conditions in the microenvironment.

  2. Host Th1/Th2 immune response to Taenia solium cyst antigens in relation to cyst burden of neurocysticercosis.

    Science.gov (United States)

    Tharmalingam, J; Prabhakar, A T; Gangadaran, P; Dorny, P; Vercruysse, J; Geldhof, P; Rajshekhar, V; Alexander, M; Oommen, A

    2016-10-01

    Neurocysticercosis (NCC), Taenia solium larval infection of the brain, is an important cause of acquired seizures in endemic countries, which relate to number, location and degenerating cysts in the brain. Multicyst infections are common in endemic countries although single-cyst infection prevails in India. Single-cyst infections in an endemic country suggest a role for host immunity limiting the infection. This study examined ex vivo CD4(+) T cells and in vitro Th1 and Th2 cytokine responses to T. solium cyst antigens of peripheral blood mononuclear cells of healthy subjects from endemic and nonendemic regions and of single- and multicyst-infected patients for association with cyst burden of NCC. T. solium cyst antigens elicited a Th1 cytokine response in healthy subjects of T. solium-endemic and T. solium-non-endemic regions and those with single-cyst infections and a Th2 cytokine response from subjects with multicyst neurocysticercosis. Multicyst neurocysticercosis subjects also exhibited low levels of effector memory CD4(+) T cells. Th1 cytokine response of T. solium exposure and low infectious loads may aid in limiting cyst number. Th2 cytokines and low effector T cells may enable multiple-cyst infections to establish and persist.

  3. A novel role of IL-17–producing lymphocytes in mediating lytic bone disease in multiple myeloma

    Science.gov (United States)

    Noonan, Kimberly; Marchionni, Luigi; Anderson, Judy; Pardoll, Drew; Roodman, G. David

    2010-01-01

    Osteoclast (OC)–mediated lytic bone disease remains a cause of major morbidity in multiple myeloma. Here we demonstrate the critical role of interleukin-17–producing marrow infiltrating lymphocytes (MILs) in OC activation and development of bone lesions in myeloma patients. Unlike MILs from normal bone marrow, myeloma MILs possess few regulatory T cells (Tregs) and demonstrate an interleukin-17 phenotype that enhances OC activation. In univariate analyses of factors mediating bone destruction, levels of cytokines that selectively induce and maintain the Th17 phenotype tightly correlated with the extent of bone disease in myeloma. In contrast, MILs activated under conditions that skew toward a Th1 phenotype significantly reduced formation of mature OC. These findings demonstrate that interleukin-17 T cells are critical to the genesis of myeloma bone disease and that immunologic manipulations shifting MILs from a Th17 to a Th1 phenotype may profoundly diminish lytic bone lesions in multiple myeloma. PMID:20664052

  4. CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization.

    Science.gov (United States)

    Livingston, Kimberly A; Jiang, Xiaowen; Stephensen, Charles B

    2013-04-30

    Routine methods for enumerating antigen-specific T-helper cells may not identify low-frequency phenotypes such as Th2 cells. We compared methods of evaluating such responses to identify tetanus toxoid- (TT) specific Th1, Th2, Th17 and IL10(+) cells. Eight healthy subjects were given a TT booster vaccination. Blood was drawn before, 3, 7, 14, and 28days after vaccination and peripheral blood mononuclear cells (PBMC) were cultured for 7days with TT, negative control (diluent), and a positive control (Staphylococcus enterotoxin B [SEB]). Activation markers (CD25 and CD69) were measured after 44h (n=8), cytokines in supernatant after 3 and 7days, and intracellular cytokine staining (ICS) of proliferated cells (identified by dye dilution) after 7days (n=6). Vaccination increased TT-specific expression of CD25 and CD69 on CD3(+)CD4(+) lymphocytes, and TT-specific proliferation at 7, 14 and 28days post vaccination. Vaccination induced TT-specific Th1 (IFN-γ, TNF-α, and IL-2) Th2 (IL-13, IL-5, and IL-4), Th17 (IL-17A) and IL-10(+) cells as measured by ICS. TT-specific Th1 cells were the most abundant (12-15% of all TT-specific CD4(+) T-cells) while IL10(+) (1.8%) Th17 (1.1%) and Th2 cells (0.2-0.6%) were less abundant. TT-specific cytokine concentrations in PBMC supernatants followed the same pattern where a TT-specific IL-9 response was also seen. In conclusion, TT booster vaccination induced a broad T-helper cell response. This method of evaluating cytokine phenotypes may be useful in examining the impact of nutrition and environmental conditions on the plasticity of T-helper cell memory responses.

  5. Lymphocyte Trafficking to Mucosal Tissues

    DEFF Research Database (Denmark)

    Mikhak, Zamaneh; Agace, William Winston; Luster, Andrew D.

    2015-01-01

    Lymphocytes are the key cells of the adaptive immune system that provide antigen-specific responses tailored to the context of antigen exposure. Through cytokine release and antibody production, lymphocytes orchestrate and amplify the recruitment and function of other immune cells and contribute...... to host defense against invading pathogens and the pathogenesis of many inflammatory diseases. Lymphocyte function is critically dependent on their ability to traffic into the correct anatomic locations at the appropriate times. This process is highly regulated and requires that lymphocytes interact...

  6. Pregnancy estrogen drives the changes of T-lymphocyte subsets and cytokines and prolongs the survival of H-Y skin graft in murine model

    Institute of Scientific and Technical Information of China (English)

    LIN Xing-guang; ZHOU Qi; WANG Li; GAO Ying; ZHANG Wei-na; LUO Zhen-long; CHEN Bi-cheng; CHEN Zhong-hua; CHANG Sheng

    2010-01-01

    Background Estrogen as well as CD4+Foxp3+ regulatory T cells were shown to have a protective role not only in maintaining maternal-fetal tolerance but also against autoimmune diseases. We aimed to investigate whether the pregnancy levels of estrogen are enough to induce transplant tolerance as to maintain fetal-maternal tolerance.Methods We established H-Y skin graft transplantation in C57BL/6 ovariectomized mice that reconstituted with estrogen. Subsequently, consecutive daily estrogen injection was administrated. Tregs and the cytokines in the peripheral blood were detected by flow cytometry and ELISA pre- and post-transplant.Results The results indicated that pregnancy levels of estrogen could promote Tregs in secondary lymphoid organs and peripheral blood (P0.05). The estrogen-treated recipients accepted H-Y skin grafts for more than 35 days (median survival time (MST): (44.0±1.2) days) compared with estrogen-untreated mice (MST:(23.0±1.6) days) (P <0.05). It was also observed that estrogen up-regulated the expression of Foxp3, but did not affect CD3+CD8+ effector T-cells in non-transplant mice. While in the presence of H-Y antigens, the expression of Foxp3 was more significant and CD3+CD8+ effector T cells were decreased significantly (P <0.05). Meanwhile, the up-regulated IL-10 and IL-4, and down-regulated IFN-Y could be observed (P <0.05).Conclusions Pregnancy levels of estrogen may promote the conversion of peripheral Tregs in secondary lymphoid organs, but show no effect on the natural Tregs production, differentiation and maturity in central lymphoid organs.Furthermore, pregnancy levels of estrogen could significantly prolong the survivals of H-Y skin grafts by the expansion of Tregs, suppression of CD3+CD8+ effector T-cells and immune shift towards Th2 cytokines.

  7. Detection of Intracellular Cytokine Production in Peripheral Blood CD3+ T Cells of Patients with Recurrent Genital Herpes

    Institute of Scientific and Technical Information of China (English)

    QIAN Qifeng(钱起丰); GUO Hongwei(郭红卫)

    2002-01-01

    Objective:To study the role of Th1fTh2 cytokines in the pathogenesis of recurrent genital herpes (RGH), and to better understand the relationship between them.Methods: A two-color immunofluorescent staining of cell surface antigen and intracellular cytokines for flow cytometric analysis was used for CD3, IL-2, IL-10, IL-12,IFN-γ and TNF-α in CD3+ T-lymphocytes in activated peripheral blood mononuclear cells of patients with RGH.Results: Compared to controls, patients with RGH showed fewer CD3+T cells (P<0.05) and IL-2 producing and IFN-γ producing T cells (P<0.02 and P<0.001, respectively)after in vitro stimulation with PMA and ionomycin in the presence of a protein transport inhibitor. More IL-10 producing and IL-12 producing T cells were found in patients with RGH (P<0.01). There was no significant difference in the number of TNF-α producing cells between RGH patients and controls (P<0.05).Conclusion: RGH patients showed relatively more Th2 cytokines. The imbalance between Th1 and Th2 cytokines results in inhibitory effects on a series of cell-immune responses, which may play an important role in the pathogenesis of RGH.

  8. RPR 106541, a novel, airways-selective glucocorticoid: effects against antigen-induced CD4+ T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung.

    Science.gov (United States)

    Underwood, S L; Raeburn, D; Lawrence, C; Foster, M; Webber, S; Karlsson, J A

    1997-10-01

    1. The effects of a novel 17-thiosteroid, RPR 106541, were investigated in a rat model of allergic airway inflammation. 2. In sensitized Brown Norway rats, challenge with inhaled antigen (ovalbumin) caused an influx of eosinophils and neutrophils into the lung tissue and airway lumen. In the lung tissue there was also an accumulation of CD4+ T lymphocytes and increased expression of mRNA for interleukin-4 (IL-4) and IL-5, but not interferon-gamma (IFN-gamma). These findings are consistent with an eosinophilia orchestrated by activated Th2-type cells. 3. RPR 106541 (10-300 microg kg[-1]), administered by intratracheal instillation into the airways 24 h and 1 h before antigen challenge, dose-dependently inhibited cell influx into the airway lumen. RPR 106541 (100 microg kg[-1]) caused a significant (PRPR 106541 was approximately 7 times and 4 times more potent than budesonide and fluticasone propionate, respectively. 4. When tested at a single dose (300 microg kg[-1]), RPR 106541 and fluticasone each caused a significant (PRPR 106541 and fluticasone (300 microg kg[-1]), but not budesonide (300 microg kg[-1]), significantly (PRPR 106541 (300 microg kg[-1]) also significantly (PRPR 106541 in this model, which mimics important aspects of airway inflammation in human allergic asthmatics, suggests that this glucocorticoid may be useful in the treatment of bronchial asthma.

  9. Immunosuppressive effect of isopropanol: down-regulation of cytokine production results from the alteration of discrete transcriptional pathways in activated lymphocytes.

    Science.gov (United States)

    Désy, Olivier; Carignan, Damien; Caruso, Manuel; de Campos-Lima, Pedro O

    2008-08-15

    Isopropanol (IPA) is widely used in household applications and constitutes a leading cause of acute alcohol intoxication second only to ethanol. Although the effects of ethanol on the immune system have been extensively studied, far fewer data are available on IPA. Given the structural similarity between the two molecules, we hypothesized that IPA could as well have immunomodulatory properties. We report here that acute IPA exposure is detrimental to human T lymphocyte and NK cell activity in vitro in concentrations as low as 0.08-0.16% (13-26 mM). IPA treatment did not affect receptor-mediated early signaling but had a reproducible and dose-dependent effect on the nuclear translocation of NFAT and AP-1. Furthermore, we show in a model of acute IPA intoxication that animals became immunosuppressed as judged by their reduced ability to release IL-2 and IFN-gamma in the serum in response to staphylococcal enterotoxin B. This effect was also associated to the down-regulation of TNF-alpha production and was sufficiently strong to rescue susceptible animals from enterotoxin-induced toxic shock. Our results suggest that IPA is potentially immunosuppressive to the adaptive and innate immune system and have broad significance given the exposure of the general population to this ubiquitous chemical.

  10. Vaccination of Mice with Salmonella Expressing VapA: Mucosal and Systemic Th1 Responses Provide Protection against Rhodococcus equi Infection

    Science.gov (United States)

    Oliveira, Aline F.; Ruas, Luciana P.; Cardoso, Silvia A.; Soares, Sandro G.; Roque-Barreira, Maria-Cristina

    2010-01-01

    Conventional vaccines to prevent the pneumonia caused by Rhodococcus equi have not been successful. We have recently demonstrated that immunization with Salmonella enterica Typhimurium expressing the VapA antigen protects mice against R. equi infection. We now report that oral vaccination of mice with this recombinant strain results in high and persistent fecal levels of antigen-specific IgA, and specific proliferation of the spleen cells of immunized mice in response to the in vitro stimulation with R. equi antigen. After in vitro stimulation, spleen cells of immunized mice produce high levels of Th1 cytokines and show a prominent mRNA expression of the Th1 transcription factor T-bet, in detriment of the Th2 transcription factor GATA-3. Following R. equi challenge, a high H2O2, NO, IL-12, and IFN-γ content is detected in the organs of immunized mice. On the other hand, TNF-α and IL-4 levels are markedly lower in the organs of vaccinated mice, compared with the non-vaccinated ones. The IL-10 content and the mRNA transcription level of TGF-β are also higher in the organs of immunized mice. A greater incidence of CD4+ and CD8+ T cells and B lymphocytes is verified in vaccinated mice. However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4+CD25+Foxp3+ T cells. Finally, we show that the vaccination confers a long-term protection against R. equi infection. Altogether, these data indicate that the oral vaccination of mice with S. enterica Typhimurium expressing VapA induces specific and long-lasting humoral and cellular responses against the pathogen, which are appropriately regulated and allow tissue integrity after challenge. PMID:20072623

  11. Vaccination of mice with salmonella expressing VapA: mucosal and systemic Th1 responses provide protection against Rhodococcus equi infection.

    Directory of Open Access Journals (Sweden)

    Aline F Oliveira

    Full Text Available Conventional vaccines to prevent the pneumonia caused by Rhodococcus equi have not been successful. We have recently demonstrated that immunization with Salmonella enterica Typhimurium expressing the VapA antigen protects mice against R. equi infection. We now report that oral vaccination of mice with this recombinant strain results in high and persistent fecal levels of antigen-specific IgA, and specific proliferation of the spleen cells of immunized mice in response to the in vitro stimulation with R. equi antigen. After in vitro stimulation, spleen cells of immunized mice produce high levels of Th1 cytokines and show a prominent mRNA expression of the Th1 transcription factor T-bet, in detriment of the Th2 transcription factor GATA-3. Following R. equi challenge, a high H2O2, NO, IL-12, and IFN-gamma content is detected in the organs of immunized mice. On the other hand, TNF-alpha and IL-4 levels are markedly lower in the organs of vaccinated mice, compared with the non-vaccinated ones. The IL-10 content and the mRNA transcription level of TGF-beta are also higher in the organs of immunized mice. A greater incidence of CD4+ and CD8+ T cells and B lymphocytes is verified in vaccinated mice. However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4+CD25+Foxp3+ T cells. Finally, we show that the vaccination confers a long-term protection against R. equi infection. Altogether, these data indicate that the oral vaccination of mice with S. enterica Typhimurium expressing VapA induces specific and long-lasting humoral and cellular responses against the pathogen, which are appropriately regulated and allow tissue integrity after challenge.

  12. Increased interleukin-4-positive lymphocytes in patients with Hashimoto's thyroiditis and concurrent non-endocrine autoimmune disorders.

    Science.gov (United States)

    Santaguida, M G; Nardo, S; Del Duca, S C; Lococo, E; Virili, C; Gargano, L; Lenti, L; Centanni, M

    2011-08-01

    A prevalent T helper type 1 (Th1) subset of lymphocytes has been described in Hashimoto's thyroiditis (HT), but whether a similar polarization may characterize HT when associated with non-endocrine autoimmune disorders (NEAD) is not known. The aim of the present study was to analyse the intracellular Th1 and Th2 distinctive cytokines in patients with isolated HT or associated with non-endocrine autoimmune disorders. Intracellular cytokine expression was assessed in peripheral blood lymphocytes (PBL) of 68 out-patients (females = 55; males = 13; median age = 6 years) with HT : 33 had isolated HT and 35 had a concurrent NEAD. The percentage of interferon (IFN)-γ and interleukin (IL)-2 Th1- and IL-4 Th2-positive cells was measured by flow cytometric analysis. We found an increased percentage of IL-2-positive cells in all patients, without differences between patients with isolated HT or associated with NEAD. IFN-γ(+) cells were also increased in both groups, but the median percentage of those with isolated HT was lower than in patients with HT+NEAD (19·0 versus 29·9%; P = 0·0082). An increased number of IL-4-positive cells was observed in three of 33 (9·1%) patients with isolated HT and in 25 of 35 patients with NEAD [71%; P lymphocytes characterizes patients with autoimmune thyroiditis who have associated non-endocrine autoimmune disorders. These findings may represent an initial tool to detect patients with autoimmune thyroiditis in which additional non-endocrine autoimmune disorders may be awaited.

  13. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

    Science.gov (United States)

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

  14. Natural killer cell activity, lymphocyte proliferation, and cytokine profile in tumor-bearing mice treated with MAPA, a magnesium aggregated polymer from Aspergillus oryzae.

    Science.gov (United States)

    Justo, G Z; Durán, N; Queiroz, M L S

    2003-08-01

    The present study examined the effects of MAPA, an antitumor aggregated polymer of protein magnesium ammonium phospholinoleate-palmitoleate anhydride, isolated from Aspergillus oryzae, on concanavalin A (Con A)-induced spleen cell proliferation, cytokine production and on natural killer (NK) cell activity in Ehrlich ascites tumor-bearing mice. The Ehrlich ascites tumor (EAT) growth led to diminished mitogen-induced expansion of spleen cell populations and total NK activity. This was accompanied by striking spleen enlargement, with a marked increase in total cell counts. Moreover, a substantial enhancement in IL-10 levels, paralleled by a significant decrease in IL-2 was observed, while production of IL-4 and interferon-gamma (IFN-gamma) was not altered. Treatment of mice with 5 mg/kg MAPA for 7 days promoted spleen cell proliferation, IL-2 production and NK cell activity regardless of tumor outgrowth. In addition, MAPA treatment markedly enhanced IFN-gamma levels and reduced IL-10 production relative to EAT mice. A 35% reduction in splenomegaly with normal number of nucleated cells was also found. Altogether, our results suggest that MAPA directly and/or indirectly modulates immune cell activity, and probably disengages tumor-induced suppression of these responses. Clearly, MAPA has an impact and may delay tumor outgrowth through immunotherapeutic mechanisms.

  15. Adhesion of ZAP-70+ chronic lymphocytic leukemia cells to stromal cells is enhanced by cytokines and blocked by inhibitors of the PI3-kinase pathway.

    Science.gov (United States)

    Lafarge, Sandrine T; Johnston, James B; Gibson, Spencer B; Marshall, Aaron J

    2014-01-01

    CLL cell survival and proliferation is enhanced through direct contact with supporting cells present in lymphoid tissues. PI3Ks are critical signal transduction enzymes controlling B cell survival and activation. PI3K inhibitors have entered clinical trials and show promising therapeutic activity; however, it is unclear whether PI3K inhibitor drugs differentially affect ZAP-70 positive versus negative CLL cells or target specific microenvironmental interactions. Here we provide evidence that CD40L+IL-4, IL-8 or IL-6 enhance adhesion to stromal cells, with IL-6 showing a selective effect on ZAP-70 positive cells. Stimulatory effects of IL-8 or IL-6 are fully reversed by PI3K inhibition, while the effects of CD40L+IL-4 are partially reversed. While CD40L+IL-4 is the only stimulation increasing CLL cell survival for all patient groups, IL-6 protects ZAP-70 positive cells from cell death induced by PI3K inhibition. Altogether, our results indicate that targeting the PI3K pathway can reverse protective CLL-microenvironment interactions in both ZAP-70 positive and negative CLL despite their differences in cytokine responsiveness.

  16. Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their Derivatives: A Systematic Review.

    Science.gov (United States)

    Asadi-Samani, Majid; Bagheri, Nader; Rafieian-Kopaei, Mahmoud; Shirzad, Hedayatollah

    2017-08-01

    Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant-based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Faithful expression of the human 5q31 cytokine cluster intransgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lacy, Dee A.; Wang, Zhi-En; Symula, Derek J.; McArthur, CliffordJ.; Rubin, Edward M.; Frazer, Kelly A.; Locksley, Richard M.

    1999-12-03

    ILs 4,5, and 13, cardinal cytokines produced by Th2 cells,are coordinately expressed and clustered in the 150-kb syntenic regions on mouse chromosome 11 and human chromosome 5q31. We analyzed two sets of human yeast artificial chromosome transgenic mice that contained the5931cytokines to assess whether conserved sequences required for their coordinate and cell-specific regulation are contained within the cytokine cluster itself. Human Il-4, IL-13, and Il-5 were expressed under Th2, but not Th1, conditions in vitro. Each of these cytokines was produced during infection with Nippostrongylus brasiliensis, a Th2 inducing stimulus, and human Il-4 was generated after activation of NK T cells in vivo.Consistently fewer cells produced the endogenous mouse cytokines in transgenic than in control mice, suggesting competition for stable expression between the mouse and human genes. These data imply the existence of both conserved trans-activating factors and cis-regulatory elements that underlie the coordinate expression and lineage specificity of the type 2 ctyokine genes in lymphocytes.

  18. Male and female NOD mice differentially express peroxisome proliferator-activated receptors and pathogenic cytokines.

    Science.gov (United States)

    Yaacob, Nik Soriani; Goh, Kenny Soen Keong; Norazmi, Mohd Nor

    2012-01-01

    The peroxisome proliferator-activated receptors (PPARs) have been implicated in regulating the immune response. We determined the relative changes in the transcriptional expression of PPAR isoforms (α, γ1 and γ2) and cytokines involved in the pathogenesis of type 1 diabetes (T1D) in the immune cells of 5 weeks, 10 weeks and diabetic male non-obese diabetic (NOD) mice compared to those of female NOD mice from our previous studies, "normalized" against their respective non-obese diabetic resistant (NOR) mice controls. Overall PPARα was significantly more elevated in the macrophages of female NOD mice of all age groups whereas PPARγ, particularly the PPARγ2 isoform was more depressed in the macrophages and CD4(+) lymphocytes of female NOD mice compared to their male counterparts. The pro-inflammatory cytokines, IL-1 and TNFα, as well as the Th1 cytokines, IL-2 and IFNγ were more elevated in female NOD mice whereas the Th2 cytokine, IL-4, was more depressed in these mice compared to their male counterparts. These findings suggest that the preponderance of T1D in female NOD mice may be influenced by the more pronounced changes in the expression of PPAR isoforms and pathogenic cytokines compared to those in male NOD mice. Copyright © 2010 Elsevier GmbH. All rights reserved.

  19. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokine...... cells mutually down-regulate each other. However, the presence of antigen specific regulatory T cell subsets may provide an environment that allows the presence of both Th1 and Th2 cells....

  20. Reduced peripheral and mucosal Tropheryma whipplei-specific Th1 response in patients with Whipple's disease.

    Science.gov (United States)

    Moos, Verena; Kunkel, Désirée; Marth, Thomas; Feurle, Gerhard E; LaScola, Bernard; Ignatius, Ralf; Zeitz, Martin; Schneider, Thomas

    2006-08-01

    Whipple's disease is a rare infectious disorder caused by Tropheryma whipplei. Major symptoms are arthropathy, weight loss, and diarrhea, but the CNS and other organs may be affected, too. The incidence of Whipple's disease is very low despite the ubiquitous presence of T. whipplei in the environment. Therefore, it has been suggested that host factors indicated by immune deficiencies are responsible for the development of Whipple's disease. However, T. whipplei-specific T cell responses could not be studied until now, because cultivation of the bacteria was established only recently. Thus, the availability of T. whipplei Twist-Marseille(T) has enabled the first analysis of T. whipplei-specific reactivity of CD4(+) T cells. A robust T. whipplei-specific CD4(+) Th1 reactivity and activation (expression of CD154) was detected in peripheral and duodenal lymphocytes of all healthy (16 young, 27 age-matched, 11 triathletes) and disease controls (17 patients with tuberculosis) tested. However, 32 Whipple's disease patients showed reduced or absent T. whipplei-specific Th1 responses, whereas their capacity to react to other common Ags like tetanus toxoid, tuberculin, actinomycetes, Giardia lamblia, or CMV was not reduced compared with controls. Hence, we conclude that an insufficient T. whipplei-specific Th1 response may be responsible for an impaired immunological clearance of T. whipplei in Whipple's disease patients and may contribute to the fatal natural course of the disease.

  1. Effects of PARP-1 Deficiency on Th1 and Th2 Cell Differentiation

    Directory of Open Access Journals (Sweden)

    M. Sambucci

    2013-01-01

    Full Text Available T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosylation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose polymerases (PARPs. Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4+ cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ+ cells as well as IFN-γ production, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases.

  2. Immunoregulatory effects on T lymphocytes by human mesenchymal stromal cells isolated from bone marrow, amniotic fluid, and placenta.

    Science.gov (United States)

    Mareschi, Katia; Castiglia, Sara; Sanavio, Fiorella; Rustichelli, Deborah; Muraro, Michela; Defedele, Davide; Bergallo, Massimiliano; Fagioli, Franca

    2016-02-01

    Mesenchymal stromal cells (MSCs) are a promising tool in cell therapies because of their multipotent, bystander, and immunomodulatory properties. Although bone marrow represents the main source of MSCs, there remains a need to identify a stem cell source that is safe and easily accessible and yields large numbers of cells without provoking debates over ethics. In this study, MSCs isolated from amniotic fluid and placenta were compared with bone marrow MSCs. Their immunomodulatory properties were studied in total activated T cells (peripheral blood mononuclear cells) stimulated with phytohemagglutinin (PHA-PBMCs). In particular, an in vitro co-culture system was established to study: (i) the effect on T-lymphocyte proliferation; (ii) the presence of T regulatory lymphocytes (Treg); (iii) the immunophenotype of various T subsets (Th1 and Th2 naïve, memory, effector lymphocytes); (iv) cytokine release and master gene expression to verify Th1, Th2, and Th17 polarization; and (v) IDO production. Under all co-culture conditions with PHA-PBMCs and MSCs (independently of tissue origin), data revealed: (i) T proliferation inhibition; (ii) increase in naïve T and decrease in memory T cells; (iii) increase in T regulatory lymphocytes; (iv) strong Th2 polarization associated with increased interleukin-10 and interleukin-4 levels, Th1 inhibition (significant decreases in interleukin-2, tumor necrosis factor-α, interferon-γ, and interleukin-12) and Th17 induction (production of high concentrations of interleukins-6 and -17); (v) indoleamine-2,3-dioxygenase mRNA induction in MSCs co-cultured with PHA-PBMCs. AF-MSCs had a more potent immunomodulatory effect on T cells than BM-MSCs, only slightly higher than that of placenta MSCs. This study indicates that MSCs isolated from fetal tissues may be considered a good alternative to BM-MSCs for clinical applications.

  3. Cytokine profile of NALT during acute stress and its possible effect on IgA secretion.

    Science.gov (United States)

    Gutiérrez-Meza, Juan Manuel; Jarillo-Luna, Rosa Adriana; Rivera-Aguilar, Victor; Miliar-García, Angel; Campos-Rodríguez, Rafael

    2017-08-01

    Stress stimuli affect the immune system responses that occur at mucosal membranes, particularly IgA secretion. It has been suggested that acute stress increases the levels of IgA and that sympathetic innervation plays an important role in this process. We herein explore in a murine model how acute stress affects the Th1/Th2/Treg cytokine balance in NALT, and the possible role of glucocorticoids in this effect. Nine-week-old male CD1 mice were divided into three groups: unstressed (control), stressed (subjected to 4h of immobilization), and stressed after pretreatment with a single dose of the corticosterone receptor antagonist RU-486. The parameters evaluated included plasma corticosterone and epinephrine, IgA levels in nasal fluid (by ELISA), the percentage of CD19(+)B220(+)IgA(+) lymphocytes and CD138(+)IgA(+) plasma cells, and the mRNA expression of heavy α chain, J chain and pIgR. Moreover, the gene and protein expression of Th1 cytokines (TNFα, IL-2 and INF-γ), Th2 cytokines (IL-4 and IL-5) and Treg cytokines (IL-10 and TGFβ) were determined in nasal mucosa. The results show that acute stress generated a shift towards the dominance of an anti-inflammatory immune response (Th2 and Treg cytokines), evidenced by a significant rise in the amount of T cells that produce IL4, IL-5 and IL-10. This immune environment may favor IgA biosynthesis by CD138(+)IgA(+) plasma cells, a process mediated mostly by glucocorticoids. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  4. Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

    DEFF Research Database (Denmark)

    Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank

    2013-01-01

    '. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months...... in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained...... changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses. © 2013 S. Karger AG, Basel....

  5. Type I IFN signaling in CD8– DCs impairs Th1-dependent malaria immunity

    Science.gov (United States)

    Haque, Ashraful; Best, Shannon E.; Montes de Oca, Marcela; James, Kylie R.; Ammerdorffer, Anne; Edwards, Chelsea L.; de Labastida Rivera, Fabian; Amante, Fiona H.; Bunn, Patrick T.; Sheel, Meru; Sebina, Ismail; Koyama, Motoko; Varelias, Antiopi; Hertzog, Paul J.; Kalinke, Ulrich; Gun, Sin Yee; Rénia, Laurent; Ruedl, Christiane; MacDonald, Kelli P.A.; Hill, Geoffrey R.; Engwerda, Christian R.

    2014-01-01

    Many pathogens, including viruses, bacteria, and protozoan parasites, suppress cellular immune responses through activation of type I IFN signaling. Recent evidence suggests that immune suppression and susceptibility to the malaria parasite, Plasmodium, is mediated by type I IFN; however, it is unclear how type I IFN suppresses immunity to blood-stage Plasmodium parasites. During experimental severe malaria, CD4+ Th cell responses are suppressed, and conventional DC (cDC) function is curtailed through unknown mechanisms. Here, we tested the hypothesis that type I IFN signaling directly impairs cDC function during Plasmodium infection in mice. Using cDC-specific IFNAR1-deficient mice, and mixed BM chimeras, we found that type I IFN signaling directly affects cDC function, limiting the ability of cDCs to prime IFN-γ–producing Th1 cells. Although type I IFN signaling modulated all subsets of splenic cDCs, CD8– cDCs were especially susceptible, exhibiting reduced phagocytic and Th1-promoting properties in response to type I IFNs. Additionally, rapid and systemic IFN-α production in response to Plasmodium infection required type I IFN signaling in cDCs themselves, revealing their contribution to a feed-forward cytokine-signaling loop. Together, these data suggest abrogation of type I IFN signaling in CD8– splenic cDCs as an approach for enhancing Th1 responses against Plasmodium and other type I IFN–inducing pathogens. PMID:24789914

  6. A subunit vaccine based on rH-NS induces protection against Mycobacterium tuberculosis infection by inducing the Th1 immune response and activating macrophages.

    Science.gov (United States)

    Liu, Yuan; Chen, Suting; Pan, Bowen; Guan, Zhu; Yang, Zhenjun; Duan, Linfei; Cai, Hong

    2016-10-01

    Mycobacterium tuberculosis (Mtb) is a Gram-positive pathogen which causes tuberculosis in both animals and humans. All tested rH-NS formulations induced a specific Th1 response, as indicated by increased production of interferon γ (IFN-γ) and interleukin 2 (IL-2) by lymphocytes in the spleen of mice which were immunized with rH-NS alone or with rH-NS and the adjuvant cyclic GMP-AMP (cGAMP). Serum from mice immunized with rH-NS with or without adjuvant also had higher levels of IL-12p40 and TNF-α, compared with those from control mice immunized with phosphate-buffered saline. Both vaccines increased protective efficacy in mice which were challenged with Mtb H37Rv, as measured by reduced relative CFU counts in the lungs. We found that rH-NS induced the production of TNF-α, IL-6, and IL-12p40, which relied on the activation of mitogen-activated protein kinases by stimulating the rapid phosphorylation of ERK1/2, p38, and JNK, and on the activation of transcription factor NF-κB in macrophages. Additionally, we also found that rH-NS could interact with TLR2 but not TLR4 in pull-down assays. The rH-NS-induced cytokine production from TLR2-silenced RAW264.7 cells was lower than that from BALB/c macrophages. Prolonged exposure (>24 h) of RAW264.7 cells to rH-NS resulted in a significant enhancement in IFN-γ-induced MHC II expression, which was not found in shTLR2-treated RAW264.7 cells. These results suggest that rH-NS is a TLR2 agonist which induces the production of cytokines by macrophages and up-regulates macrophage function.

  7. Characterization of glycolytic enzymes--rAldolase and rEnolase of Leishmania donovani, identified as Th1 stimulatory proteins, for their immunogenicity and immunoprophylactic efficacies against experimental visceral leishmaniasis.

    Science.gov (United States)

    Gupta, Reema; Kumar, Vikash; Kushawaha, Pramod Kumar; Tripathi, Chandradev Pati; Joshi, Sumit; Sahasrabuddhe, Amogh Anant; Mitra, Kalyan; Sundar, Shyam; Siddiqi, Mohammad Imran; Dube, Anuradha

    2014-01-01

    Th1 immune responses play an important role in controlling Visceral Leishmaniasis (VL) hence, Leishmania proteins stimulating T-cell responses in host, are thought to be good vaccine targets. Search of such antigens eliciting cellular responses in Peripheral blood mononuclear cells (PBMCs) from cured/exposed/Leishmania patients and hamsters led to the identification of two enzymes of glycolytic pathway in the soluble lysate of a clinical isolate of Leishmania donovani--Enolase (LdEno) and aldolase (LdAld) as potential Th1 stimulatory proteins. The present study deals with the molecular and immunological characterizations of LdEno and LdAld. The successfully cloned and purified recombinant proteins displayed strong ability to proliferate lymphocytes of cured hamsters' along with significant nitric-oxide production and generation of Th1-type cytokines (IFN-γ and IL-12) from stimulated PBMCs of cured/endemic VL patients. Assessment of their prophylactic potentials revealed ∼ 90% decrease in parasitic burden in rLdEno vaccinated hamsters against Leishmania challenge, strongly supported by an increase in mRNA expression levels of iNOS, IFN-γ, TNF-α and IL-12 transcripts along with extreme down-regulation of TGF-β, IL-4 and IL-10. However, animals vaccinated with rLdAld showed comparatively lesser prophylactic efficacy (∼ 65%) with inferior immunological response. Further, with a possible implication in vaccine design against VL, identification of potential T-cell epitopes of both the proteins was done using computational approach. Additionally, in-silico 3-D modelling of the proteins was done in order to explore the possibility of exploiting them as potential drug targets. The comparative molecular and immunological characterizations strongly suggest rLdEno as potential vaccine candidate against VL and supports the notion of its being effective T-cell stimulatory protein.

  8. Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Iris J Gonzalez-Leal

    2014-09-01

    Full Text Available Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb and L (Ctsl play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrophages play during Leishmania infection, we generated bone-marrow derived dendritic cells (BMDC and macrophages (BMM from Ctsb-/- and Ctsl-/- mice, and studied the effects of Ctsb and Ctsl deficiency on the survival of L. major in infected cells. Furthermore, the signals used by dendritic cells to instruct Th cell polarization were addressed: the expression of MHC class II and co-stimulatory molecules, and cytokine production. We found that Ctsb-/- BMDC express higher levels of MHC class II molecules than wild-type (WT and Ctsl-/- BMDC, while there were no significant differences in the expression of co-stimulatory molecules between cathepsin-deficient and WT cells. Moreover, both BMDC and BMM from Ctsb-/- mice significantly up-regulated the levels of interleukin 12 (IL-12 expression, a key Th1-inducing cytokine. These findings indicate that Ctsb-/- BMDC display more pro-Th1 properties than their WT and Ctsl-/- counterparts, and therefore suggest that Ctsb down-regulates the Th1 response to L. major. Moreover, they propose a novel role for Ctsb as a regulator of cytokine expression.

  9. Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.

    Science.gov (United States)

    Gonzalez-Leal, Iris J; Röger, Bianca; Schwarz, Angela; Schirmeister, Tanja; Reinheckel, Thomas; Lutz, Manfred B; Moll, Heidrun

    2014-09-01

    Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb) and L (Ctsl) play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrophages play during Leishmania infection, we generated bone-marrow derived dendritic cells (BMDC) and macrophages (BMM) from Ctsb-/- and Ctsl-/- mice, and studied the effects of Ctsb and Ctsl deficiency on the survival of L. major in infected cells. Furthermore, the signals used by dendritic cells to instruct Th cell polarization were addressed: the expression of MHC class II and co-stimulatory molecules, and cytokine production. We found that Ctsb-/- BMDC express higher levels of MHC class II molecules than wild-type (WT) and Ctsl-/- BMDC, while there were no significant differences in the expression of co-stimulatory molecules between cathepsin-deficient and WT cells. Moreover, both BMDC and BMM from Ctsb-/- mice significantly up-regulated the levels of interleukin 12 (IL-12) expression, a key Th1-inducing cytokine. These findings indicate that Ctsb-/- BMDC display more pro-Th1 properties than their WT and Ctsl-/- counterparts, and therefore suggest that Ctsb down-regulates the Th1 response to L. major. Moreover, they propose a novel role for Ctsb as a regulator of cytokine expression.

  10. Alkylglycerols modulate the proliferation and differentiation of non-specific agonist and specific antigen-stimulated splenic lymphocytes.

    Directory of Open Access Journals (Sweden)

    Linxi Qian

    Full Text Available Alkylglycerols (AKGs are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed that oral AKGs administration significantly increased the immune response in mice. The aim of the present study was to investigate the in vitro immunomodulatory effect of AKGs on stimulating splenic lymphocyte responses. C57BL/6 mice were immunized with hepatitis B surface antigen (HBsAg. Splenic B cells were purified and stimulated with anti-BCR and anti-CD38. Meanwhile, splenic CD4+ T cells were purified and stimulated with anti-CD3 and anti-CD28. For antigen specific stimulation, the purified CD4+ T cells were cocultured with HBsAg -pulsed dendritic cells. The stimulated lymphocytes were treated with different concentrations of AKGs. The cell proliferation was assessed by [3H]-thymidine incorporation assay. The maturation of B cells was assessed by examining the germline (GL transcription of IgG (γ1 mRNA expression, and the surface expressions of CD80/CD86 markers were examined by flow cytometry analysis. Th1/Th2 polarity was assessed by T-BET (Th1/GATA-3 (Th2 flow cytometry assay and by characteristic cytokines ELISA assay (TNF-α and IFN-γ for Th1; IL-4 and IL-10 for Th2. It was found that AKGs significantly increased the BCR/CD38 -stimulated B cell proliferation. The T cell proliferation in response to CD3/CD28 or specific antigen stimulation was also increased by AKGs. The transcriptional level of IgG (γ1 and the expressions of CD80/CD86 molecules were markedly increased by AKGs in BCR/CD38 -stimulated B cells. Meanwhile, the results showed that AKGs increased the expression of T-BET transcriptional factor and the production of Th1 cytokines (TNF-α and IFN-γ upon CD3/CD28 stimulation; whereas, levels of Th2 cytokines (IL-4 and IL-10 were decreased by AKGs. Our study demonstrated that AKGs can modulate immune responses by boosting the proliferation and maturation of murine lymphocytes in vitro.

  11. Oral administration of an immunostimulatory DNA sequence from Bifidobacterium longum improves Th1/Th2 balance in a murine model.

    Science.gov (United States)

    Takahashi, Noritoshi; Kitazawa, Haruki; Iwabuchi, Noriyuki; Xiao, Jin-Zhong; Miyaji, Kazuhiro; Iwatsuki, Keiji; Saito, Tadao

    2006-08-01

    We have reported the antiallergic activities of the immunostimulatory oligodeoxynucleotide (ODN) BL07S, identified from genomic DNA of Bifidobacterium longum BB536 from in vitro and in vivo studies. The present study evaluated the efficiency of ODN BL07S in preventing allergic responses by oral administration. Oral administration of BL07S suppressed serum ovalbumin (OVA)-specific immunoglobulin (Ig) E levels and improved the OVA-specific IgG2a/IgG1 ratio. ODN BL07S increased Th1 cytokine and decreased Th2 cytokine production in splenocytes. These results suggest that immunostimulatory ODNs are potentially associated with the antiallergic effects of probiotics.

  12. Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Daisuke; Miyamoto, Ayumi; Hattori, Yuki; Komori, Takaya [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Nakamura, Takashi [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Igarashi, Tatsuhiko, E-mail: tigarash@virus.kyoto-u.ac.jp [Laboratory of Primate Model, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Harashima, Hideyoshi, E-mail: harasima@pharm.hokudai.ac.jp [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Sugita, Masahiko, E-mail: msugita@virus.kyoto-u.ac.jp [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)

    2013-11-08

    Highlights: •Glucose monomycolate (GMM) is a marker glycolipid for active tuberculosis. •Tissue responses to GMM involved up-regulation of Th1-attracting chemokines. •Th1-skewed local responses were mounted at the GMM-injected tissue. -- Abstract: Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cell responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated with Mycobacterium bovis bacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection.

  13. Age-related differentiations of Th1/Th2 cytokines in newborn infants

    Directory of Open Access Journals (Sweden)

    Efthimia Protonotariou

    2004-01-01

    Full Text Available OBJECTIVE: To evaluate age-related differentiation of immune response in newborns by measuring serum concentrations of interleukin-2 (IL-2, interleukin-4 (IL-4 and interferon-γ (IFN-γ during the perinatal period.

  14. Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract

    Science.gov (United States)

    Aeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus,. Microarray profiling of...

  15. Th1/Th2 Cytokines: An Easy Model to Study Gene Expression in Immune Cells

    Science.gov (United States)

    Moran, Jose M.; Gonzalez-Polo, Rosa A.; Soler, German; Fuentes, Jose M.

    2006-01-01

    This report describes a laboratory exercise that was incorporated into a Cell Biology and Molecular Biology advanced course. The exercise was made for a class size with eight students and was designed to reinforce the understanding of basic molecular biology techniques. Students used the techniques of reverse transcription and arginase activity…

  16. Increased intracellular Th1 cytokines in scid mice with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Bregenholt, S; Claesson, Mogens Helweg

    1998-01-01

    by intracellular staining. A 4-5-fold increase in the fraction of IFN-gamma-producing CD4+ lamina propria T cells was found in moderately and severely diseased mice when compared to healthy congenic C.B-17 control mice. The number of IL-2-producing T cells was increased by approximately 2-fold when comparing mice...

  17. Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard.

    Science.gov (United States)

    Badr, Mostafa Z; Shnyra, Alexander; Zoubine, Mikhail; Norkin, Maxim; Herndon, Betty; Quinn, Tim; Miranda, Roberto N; Cunningham, Michael L; Molteni, Agostino

    2007-01-01

    Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines, we investigated the impact of activating these receptors on hepatic pathology associated with a well-characterized model of Th1-type pulmonary response. Male Fischer 344 rats were either maintained on a drug-free diet (groups I and II), or a diet containing diethylhexylphthalate (DEHP), a compound transformed in vivo to metabolites known to activate PPARs, for 21 days (groups III and IV). Subsequently, animals were primed with Mycobacterium bovis purified protein derivative (PPD) in a Complete Freund's Adjuvant. Fifteen days later, animals in groups II and IV were challenged with Sepharose 4B beads covalently coupled with PPD, while animals in groups I and III received blank Sepharose beads. Animals with Th1 response (group II) showed a marked structural disruption in the hepatic lobule. Remarkably, these alterations were conspicuously absent in animals which received DEHP (group IV), despite noticeable accumulation of T cells in the periportal triads. Immunostaining and confocal microscopy revealed hepatic accumulation of IFNgamma+ Th1 and IL-4+ Th2 cells in animals from groups II and IV, respectively. Our data suggest a PPARalpha-mediated suppression of the development of a Th1 immune response in the liver, resulting in hepatoprotective effect. However, potentially negative consequences of PPAR activation, such as decreased ability of the immune system to fight infection and interference with the efficacy of vaccines designed to evoke Th1 immune responses, remain to be investigated.

  18. Cytokines gene expression in newly diagnosed multiple sclerosis patients.

    OpenAIRE

    Seyed Javad Hasheminia; Sepideh Tolouei; Sayyed Hamid Zarkesh-Esfahani; Vahid Shaygannejad; Hedaiat Allah Shirzad; Reza Torabi; Morteza Hashem Zadeh Chaloshtory

    2015-01-01

    Multiple Sclerosis (MS) is characterized by multiple areas of inflammation, demyelination and neurodegeneration. Infiltrating Th1 CD4+ T cells secrete proinflammatory cytokines. They stimulate the release of some cytokines, expression of adhesion molecules and these cytokines may cause damage to the myelin sheath and axons. In this study, we analyzed plasma levels and gene expressions of five important cytokines in the new diagnosed MS Patients by ELISA and Real time PCR. PCR amplifications w...

  19. Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Nilesh Dharajiya

    Full Text Available According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1, Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1 Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2 Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation.

  20. Use of flow cytometry to investigate the cytokine response pattern in infants with respiratory syncytial virus infection and bronchiolitis

    Institute of Scientific and Technical Information of China (English)

    陈志敏; 杜立中; 毛建华; 汤永民

    2002-01-01

    Objective: To investigate the cytokine response pattern (IL-4/IFN-γ) in infants with RSV infections and bronchiolitis during the acute phase. Methods: Four-color flow cytometry was used to measure intracellular IL-4 and IFN-γ expressions in peripheral blood CD3+ and CD8+ lymphocytes from RSV-infected and bronchiolitis infants. Serum IL-4 and IFN-γ levels were also determined. Results: RSV-infected and bronchiolitis infants showed no statistical differences from not-RSV-infected or pneumonia infants and control in the frequency of IL-4 and IFN-γ expressions in CD3+CD8- lymphocytes, showed no obvious Th1/Th2 imbalance, while IFN-γ was expressed much more frequently in CD3+CD8+ lymphocytes. Systematically, RSV-infected and bronchiolitis infants showed much lower levels of serum IL-4 and IL-4/IFN-γ ratios and much higher serum IFN-γ levels than control. However, there were no statistical differences in the above three indices between RSV-infected and not-RSV infected infants or between bronchiolitis and pneumonia infants, except that bronchiolitis infants had a higher level of serum IFN-γ than pneumonia infants statistically. Conclusions: There is no type-2 cytokine response predominance in the acute phase of RSV infection and bronchiolitis. IL-4 production is suppressed and IFN-γ production upregulated, the latter being most prominent in bronchiolitis infants.

  1. Modelo natural de dicotomía TH1-TH2: La enfermedad de Hansen Th1-TH2 balance. Natural model: Hansen'disease

    Directory of Open Access Journals (Sweden)

    N. L Vaquero

    2010-09-01

    . Either polars forms present a defwed citokynes secretion profile: Th1 cells (IL-2 and IFN-g dominate in tuberculoid form, whereas cytokines typically produced by Th2 cells (IL-4, IL-5 and IL-10 dominate in lepromatous form. In the first case, the macrophagic activation kills M leprae. It's lesions are located in nerves and skin only. In the second case, cell-mediated immunity is absent. The bacilli multiply uncontrolably in macrophages and infection is widely disseminated affecting other organs. Humoral immunity is exacerbated and have high levels of antibodies that cannot reach intracellular germ. The factors that determine whether the proliferation CD 4 T cells differentiate into Th1 or Th2 cell are not fully understood. Several hypothesis include genetics factors, prevail of cytokinesin the microenviroment, macrophagic disfunction; alterations in the coestimulatory molecules, on toll receptors of the innate immunity, etc. In recent years times new limphocytes subsets have been discovery (CD4+CD 25+, Tr1, Th3, Th17 that could be implicated in this desregulated immune reponses.

  2. Epidemiology of Hepatitis B, C, D and G Viruses and Cytokine Levels among Intravenous Drug Users

    Institute of Scientific and Technical Information of China (English)

    LI Jianrong; WANG Jing; TIAN Kunlun; WANG Yixin; ZHANG Lei; HUANG Hanju

    2006-01-01

    To investigate the features of various hepatitis virus infection in intravenous drug users (IVDU), we conducted an epidemiological survey of hepatitis viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis G virus (HGV) in IVDU. The correlation of TH lymphocyte cytokine and hepatitis virus infection was examined. A study population of 406 IVDU consisted of 383 males and 23 females. HBV-DNA and HCV-RNA were detected by fluorescence quantitative polymerase chain reaction. HBsAg, HBeAg, anti-HBc,anti-HCV, HDV-Ag and anti-HGV were assayed by ELISA. The levels of cytokines of TH 1 and TH2 were measured by ELISA. The similar indices taken from 102 healthy persons served as controls. The infection-rate of each virus among IVDU was 36.45 % for HBV, 69. 7 % for HCV,2.22 % for HDV, and 1. 97 % for HGV, respectively. The co-infection rate of HBV and HCV was detected in 113 of 406 (27. 83%). In contrast, among controls, the infection rate was 17.65 % for HBV and 0% for the other hepatitis viruses. The levels of PHA-induced cytokines (IFN-γ and IL-4) and the level of serum IL 2 were obviously decreased in IVDU. On the other hand, the level of serum IL-4 was increased. The IFN-γ level was continuously decreased when the IVDU was infected with HBV/HCV. In conclusion, HBV and HCV infection were common in this population ofIVDU and they had led to a high incidence of impaired TH 1 cytokine levels.

  3. Respuesta inmune Th1 en la osteoartritis de la articulación temporomandibular Th1 Immune Response in Osteoarthritis of the Temporomandibular Joint

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    R Vernal

    2007-04-01

    Full Text Available Propósito. La osteoartritis temporomandibular es una enfermedad articular degenerativa, caracterizada por la destrucción del cartílago y hueso articular consecutiva a la respuesta inflamatoria e inmune desarrollada. En el presente trabajo se evalúa la expresión a nivel de ARN mensajero de diversas citoquinas proinflamatorias en los sinoviocitos articulares de individuos afectados por osteoartritis temporomandibular. Material y métodos. En 12 pacientes afectados de osteoartritis temporomandibular y en 6 sujetos sanos se evaluó la expresión de citoquinas en sinoviocitos de la articulación temporomandibular mediante la técnica de PCR cuantitativa en tiempo real. Resultados. Significativamente mayores niveles de IL-1beta, IL-2, IL-12, IL-17, TNFalfa, TNFbeta e IFNgamma fueron observados en pacientes afectados de osteoartritis temporomandibular en comparación a sujetos sanos. En los sujetos enfermos la citoquina predominante fue IL-12 y en los sanos fue IL-10. Conclusión. Tomados en conjunto, nuestros datos demuestran una asociación de elevados niveles de citoquinas propias de una respuesta inmune Th1 y la destrucción observada durante la osteoartritis temporomandibular.Background. Temporomandibular osteoarthritis is a degenerative disease that affects the temporomandibular joint and is characterized by the cartilage and bone destruction caused by the inflammatory and immune response. This communication reports on the expression of proinflammatory cytokines in synovial cells of patients with temporomandibular osteoarthritis. Methods. In twelve temporomandibular osteoarthritis patients and six healthy control subjects, cytokine expression in synovial cells was evaluated by quantitative PCR. Results. Levels of IL-1beta, IL-2, IL-12, IL-17, TNFalpha, TNFbeta e IFNgamma were significantly higher in synovial cells of patients than in controls. In particular, IL-12 was the predominant cytokine in patients and IL-12 in healthy subjects

  4. Curcumin regulated shift from Th1 to Th2 in trinitrobenzene sulphonic acid-induced chronic colitis

    Institute of Scientific and Technical Information of China (English)

    Ming ZHANG; Chang-sheng DENG; Jia-ju ZHENG; Jian XIA

    2006-01-01

    Aim: To investigate the therapeutic effects of curcumin (Cur) on trinitrobenzene sulphonic acid (TNBS)-induced colitis and the effects of Cur on the balance of Th1/Th2 cytokines. Methods: Colitis was induced by TNBS and treated with Cur (30 mg·kg-1·d-1, ip), dexamethasone (Dex, 2 mg·kg-1·d-1), or Cur plus dexamethasone (Cur+Dex, 30 mg·kg-1·d-1 Cur ip+2 mg·kg-1·d-1 Dex, ip). mRNA in colon mucosa were detected by real-time quantitative polymerase chain reaction. Intracellular cytokines were detected by flow cytometry and concentrations of cytokines in sera were detected by enzyme-linked immunosorbent analysis. Results: Both Cur and Dex improved body weight loss, ameliorated histological images and decreased macroscopic score and myeloperoxidase activity. Cur decreased the expression of Thl cytokines (IL-12, IFN-γ, TNF-α, IL-1) and increased the expression of Th2 cytokines (IL-4 and IL-10) in colon mucosa. Cur also increased the proportion of IFN-γ/IL-4 in splenocytes and circulation. Dex and Cur+Dex decreased the expression of Thl cytokines but could not increase the expression of Th2 cytokines and the proportion of IFN-γ/IL-4. Conclusion: Cur exerted therapeutic effects on colitis by regulating the shift from Thl to Th2.

  5. Rhodiola rosea suppresses thymus T-lymphocyte apoptosis by downregulating tumor necrosis factor-α-induced protein 8-like-2 in septic rats.

    Science.gov (United States)

    Liu, Ming-Wei; Su, Mei-Xian; Zhang, Wei; Zhang, Lin-Ming; Wang, Yun-Hui; Qian, Chuan-Yun

    2015-08-01

    In recent years, several studies have shown that Rhodiola rosea can enhance cellular immunity and humoral immune function in mice, and thus, it has become a research hotspot. However, its underlying mechanism of action has remained elusive. The present study investigated whether Rhodiola rosea was able to downregulate the expression of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2), thereby inhibiting the expression of apoptotic genes, attenuating T-lymphocyte apoptosis and improving immunity in septic mice. A mouse model of caecal ligation and puncture (CLP)-induced sepsis was established, and animals in the treatment group were pre-treated with an intraperitoneal injection of Rhodiola rosea extract, while animals in the control group and sham-operated group were injected with an equivalent amount of normal saline. TIPE2, B-cell lymphoma 2 (Bcl-2), Fas and Fas ligand (FasL) mRNA and protein levels in thymic T cells were determined using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. Furthermore, the thymus T-lymphocyte apoptosis rate, thymus T-lymphocyte count and thymus T-lymphocyte sub-sets were assessed using flow cytometry. Levels of T-helper cell type 1 (Th1) cytokines [Interleukin (IL)-2, IL-12 and interferon (IFN)-γ] and Th2 cytokines (IL-4 and IL-10) were determined using ELISA. The results showed that, compared to that in the CLP group, the expression of TIPE2, Fas and FasL in the treatment group was significantly decreased, while the expression of Bcl-2 was increased (Pthymus lymphocyte count in the CLP group was significantly higher compared with that in the treatment group (Pthymus T-lymphocytes in the treatment group was significantly lower than that in the CLP group (Pthymus T lymphocytes in the CLP group (Pthymus index of septic mice treated with Rhodiola rosea as well as their survival rate were improved as compared with those in the CLP group. These findings suggested that

  6. Effector molecules released by Th1 but not Th17 cells drive an M1 response in microglia.

    Science.gov (United States)

    Prajeeth, Chittappen K; Löhr, Kirsten; Floess, Stefan; Zimmermann, Julian; Ulrich, Reiner; Gudi, Viktoria; Beineke, Andreas; Baumgärtner, Wolfgang; Müller, Marcus; Huehn, Jochen; Stangel, Martin

    2014-03-01

    Microglia act as sensors of inflammation in the central nervous system (CNS) and respond to many stimuli. Other key players in neuroinflammatory diseases are CD4+ T helper cell (Th) subsets that characteristically secrete IFN-γ (Th1) or IL-17 (Th17). However, the potential of a distinct cytokine milieu generated by these effector T cell subsets to modulate microglial phenotype and function is poorly understood. We therefore investigated the ability of factors secreted by Th1 and Th17 cells to induce microglial activation. In vitro experiments wherein microglia were cultured in the presence of supernatants derived from polarized Th1 or Th17 cultures, revealed that Th1-associated factors could directly activate and trigger a proinflammatory M1-type gene expression profile in microglia that was cell-cell contact independent, whereas Th17 cells or its associated factors did not have any direct influence on microglia. To assess the effects of the key Th17 effector cytokine IL-17A in vivo we used transgenic mice in which IL-17A is specifically expressed in astrocytes. Flow cytometric and histological analysis revealed only subtle changes in the phenotype of microglia suggesting only minimal effects of constitutively produced IL-17A on microglia in vivo. Neither IL-23 signaling nor addition of GM-CSF, a recently described effector molecule of Th17 cells, changed the incapacity of Th17 cells to activate microglia. These findings demonstrate a potent effect of Th1 cells on microglia, however, the mechanism of how Th17 cells achieve their effect in CNS inflammation remains unclear.

  7. [Cytokines and asthma].

    Science.gov (United States)

    Gani, F; Senna, G; Piglia, P; Grosso, B; Mezzelani, P; Pozzi, E

    1998-10-01

    Asthma is a chronic inflammatory lung disease in which eosinophils are one of the most important involved cells. These cells accumulate in the lung because of cytokines, which are able to regulate cellular responses. The role of cytokines is well known in allergic asthma: IL4, IL5, IL3, GMCSF are the principally cytokine involved. IL4 regulate IgE synthesis while IL5, (and IL3) cause the activation and accumulation of eosinophils. In non allergic asthma, whilst only IL5 seemed to be important recent data, shows that also IL4 plays an important role. Therefore nowadays no relevant difference seems to exist between allergic and non allergic asthma; instead the primer is different: the allergen in allergic asthma and often an unknown factor in the non allergic asthma. Recently other cytokines have been proved to play a role in the pathogenesis of asthma. IL8 is chemotactic not only for neutrophils but also for eosinophils and might cause chronic inflammation in severe asthma. IL13 works like IL4, while RANTES seems to be a more important chemotactic agent than IL5. Finally IL10, which immunoregulates T lymphocyte responses, may reduce asthma inflammation. In conclusion cytokine made us to learn more about the pathogenesis of asthma even if we do not yet know when and how asthma inflammation develops.

  8. Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Jia He; Xiao-Feng Tang; Qiu-Yan Chen; Hai-Qiang Mai; Zhou-Feng Huang; Jiang Li; Yi-Xin Zeng

    2012-01-01

    Establishing Epstein-Barr virus (EBV)-specific cytolytic T lymphocytes (EBV-CTLs) from peripheral blood mononuclear cells (PBMCs) for adoptive immunotherapy has been reported in EBV-associated malignancies including Hodgkin's lymphoma and nasopharyngeal carcinoma (NPC).In the current study,we performed ex vivo expansion of tumor-infiltrating lymphocytes (TILs) obtained from NPC biopsy specimens with a rapid expansion protocol using anti-CD3 monoclonal antibody (OKT3),recombinanthuman interleukin (IL)-2,and irradiated PBMCs from healthy donors to initiate the growth of TILs.Young TIL cultures comprised of more than 90% of CD3+ T cells,a variable percentage of CD3+CD8+ and CD3+CD4+ T cells,and less than 10% of CD3-CD16+ natural killer cells,a similar phenotype of EBV-CTL cultures from PBMCs.Interestingly,TIL cultures secreted high levels of the Th1 cytokines,interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α),and low levels of the Th2 cytokines,IL-4 and IL10.Moreover,young TILs could recognize autologous EBV-transformed B lymphoblast cell lines,but not autologous EBV-negative blast cells or allogeneic EBV-negative tumor cells.Taken together,these data suggest that ex vivo expansion of TILs from NPC biopsy tissue is an appealing alternative method to establish T cell-based immunotherapy for NPC.

  9. Suppressive effects of fisetin on mice T lymphocytes in vitro and in vivo.

    Science.gov (United States)

    Song, Bocui; Guan, Shuang; Lu, Jing; Chen, Zhibao; Huang, Guoren; Li, Gen; Xiong, Ying; Zhang, Shuang; Yue, Zhanpeng; Deng, Xuming

    2013-11-01

    Most of the immunosuppressive drugs have satisfactory therapeutic effects on organ transplantation and autoimmune disease. However, their clinical application is limited by side effects. Therefore, new and safe immunosuppressive drugs against acute and chronic rejections are eagerly awaited. Fisetin, a flavonoid present in various types of vegetables and fruits, has few side effects and low level of toxicity, which would be a desirable clinical feature. In the present study, we investigated the immunosuppressive effects and underlying mechanisms of fisetin against T-cell activation in vitro and in vivo. We measured the effect of fisetin on T-lymphocyte proliferation, T-cell subsets, cell cycle progression, cytokine production, and nuclear factor activation in vitro, as well as its influence on T cell-mediated delayed-type hypersensitivity reaction in vivo. In vitro, the results showed that fisetin significantly suppressed mouse splenocytes proliferation, Th1 and Th2 cytokine production, cell cycle and the ratio of CD4(+)/CD8(+) T cells. Furthermore, fisetin exerts an immunosuppressive effect in mouse T lymphocytes through the suppression of nuclear factor kappa B activation and nuclear factor of activated T cells signaling in a dose-dependent manner. In vivo, fisetin treatment also significantly inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reactions in mice. Fisetin had strong immunosuppressive activity in vitro and in vivo, suggesting a potential role for fisetin as an immunosuppressive agent. Copyright © 2013. Published by Elsevier Inc.

  10. IL-1β promotes the differentiation of polyfunctional human CCR6+CXCR3+ Th1/17 cells that are specific for pathogenic and commensal microbes.

    Science.gov (United States)

    Duhen, Thomas; Campbell, Daniel J

    2014-07-01

    In humans, Th1/17 cells, identified by coexpression of the chemokine receptors CCR6 and CXCR3, are proposed to be highly pathogenic in several autoimmune disorders due in part to their expression of the proinflammatory cytokines IL-17, IFN-γ, and GM-CSF. However, their developmental requirements, relationship with "classic" Th17 and Th1 cells and physiological role in normal immune responses are not well understood. In this study, we examined CCR6+ CXCR3+ Th1/17 cells from healthy individuals and found that ex vivo these cells produced the effector cytokines IL-17, IL-22, and IFN-γ in all possible combinations and were highly responsive to both IL-12 and IL-23. Moreover, although the Ag specificity of CCR6+ CXCR3+ Th1/17 cells showed substantial overlap with that of Th1 and Th17 cells, this population was enriched in cells recognizing certain extracellular bacteria and expressing the intestinal homing receptor integrin β7. Finally, we identified IL-1β as a key cytokine that renders Th17 cells sensitive to IL-12, and both cytokines together potently induced the differentiation of cells that produce IL-17, IFN-γ, and GM-CSF. Therefore, interfering with IL-1β and IL-12 signaling in Th17 cells during inflammation may be a promising therapeutic approach to reduce their differentiation into "pathogenic" CCR6+ CXCR3+ Th1/17 cells in patients with autoimmune diseases. Copyright © 2014 by The American Association of Immunologists, Inc.

  11. Parasite Antigen-Specific Regulation of Th1, Th2, and Th17 Responses in Strongyloides stercoralis Infection.

    Science.gov (United States)

    Anuradha, Rajamanickam; Munisankar, Saravanan; Dolla, Chandrakumar; Kumaran, Paul; Nutman, Thomas B; Babu, Subash

    2015-09-01

    Chronic helminth infections are known to be associated with modulation of Ag-specific CD4(+) T responses. However, the role of CD4(+) T cell responses in human infection with Strongyloides stercoralis is not well defined. To examine the role of CD4(+) T cells expressing Th1, Th2, and Th17 cytokines in strongyloidiasis, we compared the frequency (Fo) of these subsets in infected (INF) individuals with Fo in S. stercoralis-uninfected (UN) individuals. INF individuals exhibited a significant decrease in the spontaneous and Ag-specific Fo of both monofunctional and dual-functional Th1 cells compared with UN. Similarly, INF individuals also exhibited significantly decreased Fo of monofunctional and dual-functional Th17 cells upon Ag stimulation compared with UN. In contrast, both the spontaneous and the Ag-induced Fo of monofunctional and dual-functional Th2 cells was significantly increased in INF compared with UN individuals. This differential T cell response was predominantly Ag specific because it was abrogated upon control Ag or mitogen stimulation. The regulation of Th1, Th2, and Th17 cells was predominantly dependent on IL-10, whereas the regulation of Th2, but not Th1 or Th17, cells was also dependent on TGF-β. In addition, treatment of S. stercoralis infection significantly increased the Ag-specific Fo of Th1 and Th17 cells and decreased the Fo of Th2 cells in INF individuals. Thus, S. stercoralis infection is characterized by a parasite Ag-dependent regulation of monofunctional and dual-functional Th1, Th2, and Th17 cells, a regulation also reversible by antihelminthic treatment.

  12. Lithocholic acid controls adaptive immune responses by inhibition of Th1 activation through the Vitamin D receptor

    Science.gov (United States)

    Puchner, Teresa; Korkmaz, H. Inci; Vos, Mariska; Soeters, Maarten R.; de Vries, Carlie J. M.

    2017-01-01

    Bile acids are established signaling molecules next to their role in the intestinal emulsification and uptake of lipids. We here aimed to identify a potential interaction between bile acids and CD4+ Th cells, which are central in adaptive immune responses. We screened distinct bile acid species for their potency to affect T cell function. Primary human and mouse CD4+ Th cells as well as Jurkat T cells were used to gain insight into the mechanism underlying these effects. We found that unconjugated lithocholic acid (LCA) impedes Th1 activation as measured by i) decreased production of the Th1 cytokines IFNγ and TNFαα, ii) decreased expression of the Th1 genes T-box protein expressed in T cells (T-bet), Stat-1 and Stat4, and iii) decreased STAT1α/β phosphorylation. Importantly, we observed that LCA impairs Th1 activation at physiological relevant concentrations. Profiling of MAPK signaling pathways in Jurkat T cells uncovered an inhibition of ERK-1/2 phosphorylation upon LCA exposure, which could provide an explanation for the impaired Th1 activation. LCA induces these effects via Vitamin D receptor (VDR) signaling since VDR RNA silencing abrogated these effects. These data reveal for the first time that LCA controls adaptive immunity via inhibition of Th1 activation. Many factors influence LCA levels, including bile acid-based drugs and gut microbiota. Our data may suggest that these factors also impact on adaptive immunity via a yet unrecognized LCA-Th cell axis. PMID:28493883

  13. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  14. Cytokines and pregnancy in rheumatic disease.

    Science.gov (United States)

    Østensen, Monika; Förger, Frauke; Villiger, Peter M

    2006-06-01

    Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy-related disorders. Studies at the level of the maternal-fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study.

  15. Evidence for mouse Th1- and Th2-like helper T cells in vivo. Selective reduction of Th1-like cells after total lymphoid irradiation

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    Bass, H.; Mosmann, T.; Strober, S. (Stanford Univ. School of Medicine, CA (USA))

    1989-11-01

    Purified CD4+ BALB/c spleen T cells obtained 4-6 wk after total lymphoid irradiation (TLI) helped normal syngeneic B cells to produce a vigorous antibody response to TNP keyhole limpet hemocyanin in adoptive cell transfer experiments. However, the same cells failed to transfer delayed-type hypersensitivity to the adoptive hosts as measured by a foot pad swelling assay. In addition, purified CD4+ cells from TLI-treated mice were unable to induce graft vs. host disease in lethally irradiated allogeneic C57BL/Ka recipient mice. In response to mitogen stimulation, unfractionated spleen cells obtained from TLI mice secreted normal levels of IL-4 and IL-5, but markedly reduced levels of IL-2 and INF-gamma. A total of 229 CD4+ clones from spleen cells of both normal and TLI-treated mice were established, and the cytokine secretion pattern from each clone was analyzed. The results demonstrate that the ratio of Th1- and Th2-like clones in the spleens of normal BALB/c mice is 1:0.6, whereas the ratio in TLI mice is approximately 1:7. These results suggest that Th2-like cells recover rapidly (at approximately 4-6 wk) after TLI treatment and account for the early return of antibody helper activity and secretion of IL-4 and IL-5, but Th1-like cells recover more slowly (in approximately 3 mo) after irradiation, and this accounts for the deficit in cell-mediated immunity and the reduced amount of IL-2 and IFN-gamma secretion.

  16. Dehydrodiconiferyl alcohol (DHCA) modulates the differentiation of Th17 and Th1 cells and suppresses experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Lee, Junghun; Choi, Jinyong; Lee, Wonwoo; Ko, Kyeongryang; Kim, Sunyoung

    2015-12-01

    Dehydrodiconiferyl alcohol (DHCA), originally isolated from the stems of Cucurbita moschata, has previously been shown to exhibit anti-adipogenic and anti-lipogenic effects in 3T3-L1 cells and primary mouse embryonic fibroblasts (MEFs) (Lee et al., 2012). Here, we investigated whether synthetic DHCA could suppress the CD4 T helper 17 (Th17)-mediated production of the interleukin (IL)-17 protein. The results from RT-qPCR suggest that DHCA-mediated down-regulation of IL-17 occurred at the transcriptional level by suppressing the expression of RAR-related orphan receptor (ROR)γt, the master transcription factor involved in the differentiation of Th17 cells. Furthermore, such inhibition was mediated by the suppression of NF-κB activity. DHCA also inhibited the Th1-mediated production of interferon (IFN) γ by controlling the expression of a key transcription factor known to regulate the production of this cytokine, T-bet. In the mouse experimental autoimmune encephalomyelitis (EAE) model, DHCA showed significant therapeutic effects by inhibiting the infiltration of immune cells into the spinal cords, decreasing the differentiation of pathogenic Th17 and Th1 cells, suppressing the expression of various pro-inflammatory cytokines, and eventually ameliorating the clinical symptoms of EAE mice. Taken together, our data indicate that DHCA may be a potential candidate as an agent for the control of Th17 and Th1-mediated inflammatory diseases.

  17. Avian cytokines in health and disease

    Directory of Open Access Journals (Sweden)

    P Wigley

    2003-04-01

    Full Text Available Cytokines are proteins secreted by cells that play an important role in the activation and regulation of other cells and tissues during inflammation and immune responses. Although well described in several mammalian species, the role of cytokines and other related proteins is poorly understood in avian species. Recent advances in avian genetics and immunology have begun to allow the exploration of cytokines in health and disease. Cytokines may be classified in a number of ways, but may be conveniently arranged into four broad groups on the basis of their function. Proinflammatory cytokines such as interleukin-6 and interleukin-1beta play a role in mediating inflammation during disease or injury. Th1 cytokines, including interleukin-12 and interferon-gamma, are involved in the induction of cell-mediated immunity, whereas Th2 cytokines such as interleukin-4 are involved in the induction of humoral immunity. The final group Th3 or Tr cytokines play a role in regulation of immunity. The role of various cytokines in infectious and non-infectious diseases of chickens and turkeys is now being investigated. Although there are only a few reliable ELISAs or bioassays developed for avian cytokines, the use of molecular techniques, and in particular quantitative RT-PCR (Taqman has allowed investigation of cytokine responses in a number of diseases including salmonellosis, coccidiosis and autoimmune thyroiditis. In addition the use of recombinant cytokines as therapeutic agents or as vaccine adjuvants is now being explored.

  18. IFNbeta-1a treatment and reestablishment of Th1 regulation in MS patients: dose effects.

    Science.gov (United States)

    Pellegrini, Patrizia; Totaro, Rocco; Contasta, Ida; Berghella, Anna Maria; Russo, Tomassina; Carolei, Antonio; Adorno, Domenico

    2004-01-01

    The authors evaluated the relationships between clinical and pharmacologic parameters and the Th1/Th2/Th3 cytokine network in patients with relapsing-remitting multiple sclerosis treated with differing doses of interferon-beta1a (IFN-beta1a). Their results show that low doses are ineffective but that high doses restore Th1 regulation of the maturation and activation of monocytes, T cells, immature dendritic cells, dendritic cells, and T regulatory cells for central and peripheral self-tolerance. Interaction between interleukin (IL)-10, IL-12 p70, and IL-6 production appears to play an important role in the control of the maturation and activation states of dendritic cells and T regulatory cells, and is at the basis of the benefit of high doses. The results also indicate that the physiologic mechanisms involved in aging help immunologic reestablishment in IFNbeta-1a-treated patients. Finally, it would appear that the failure of IFNbeta-1a therapy to resolve multiple sclerosis completely is due to the suppression of IL-12 p70 mechanisms (responsible for the physiologic deletion of self-reactive cells) in activation conditions, probably by IFNbeta-1a itself.

  19. D-pinitol inhibits Th1 polarization via the suppression of dendritic cells.

    Science.gov (United States)

    Lee, Jun Sik; Jung, In Duk; Jeong, Young-Il; Lee, Chang-Min; Shin, Yong Kyoo; Lee, Sang-Yull; Suh, Dong-Soo; Yoon, Man-Soo; Lee, Kyu-Sub; Choi, Yung Hyun; Chung, Hae Young; Park, Yeong-Min

    2007-06-01

    d-pinitol has been demonstrated to exert insulin-like and anti-inflammatory effects. However, the effects of the maturation and immunostimulatory functions of dendritic cells (DC) remain to be clearly elucidated. In this study, we have attempted to determine whether d-pinitol regulates surface molecule expression, cytokine production, endocytosis capacity, and underlying signaling pathways in murine bone marrow-derived DC. We also attempted to ascertain whether d-pinitol could influence Th1/Th2 immune response in vivo. The DC used in this study were derived from murine bone marrow cells, and were used as immature or LPS-stimulated mature DC. The DC were then assessed with regard to surface molecule expression, dextran-FITC uptake, cytokine production, capacity to induce T-cell differentiation, and underlying signaling pathways. d-pinitol was shown to significantly inhibit CD80, CD86, MHC class I, and MHC class II expression in the LPS-stimulated mature DC. The DC also evidenced impaired IL-12 expression and IFN-gamma production. The d-pinitol-treated DC were found to be highly efficient in regards to Ag capture via mannose receptor-mediated endocytosis. d-pinitol was also demonstrated to inhibit LPS-induced MAPKs activation and NF-kappaB nuclear translocation. Moreover, the d-pinitol-treated DC manifested impaired induction of Th1 responses, and normal cell-mediated immune responses. These novel findings provide new insight into the immunopharmacological role of d-pinitol in terms of its effects on DC. These findings also broaden current perspectives concerning our understanding of the immunopharmacological functions of d-pinitol, and have ramifications for the development of therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.

  20. Submerged cultivation of Ganoderma lucidum and the effects of its polysaccharides on the production of human cytokines TNF-α, IL-12, IFN-γ, IL-2, IL-4, IL-10 and IL-17.

    Science.gov (United States)

    Habijanic, Jožica; Berovic, Marin; Boh, Bojana; Plankl, Mojca; Wraber, Branka

    2015-01-25

    An original strain of Ganoderma lucidum (W.Curt.:Fr.) Lloyd, MZKI G97 isolated from Slovenian habitats was grown by a submerged liquid substrate cultivation in a laboratory stirred tank reactor. Five fractions of extracellular and cell-wall polysaccharides were obtained by extraction, ethanol precipitation, and purification by ion-exchange, gel and affinity chromatography. The capacity of isolated polysaccharide fractions to induce innate inflammatory cytokines, and to modulate cytokine responses of activated lymphocytes was investigated. Human peripheral blood mononuclear cells (PBMC) were activated in vitro with polysaccharide fractions, in order to induce innate inflammatory cytokines: tumor necrosis factor alpha (TNF-α), interleukin (IL) 12 and interferon gamma (IFN-γ). For the immunomodulation capacity, polysaccharide fractions were cultured with ionomycine and phorbol myristate acetate (IONO+PMA) activated PBMC, and the concentrations of induced IL-2, IL-4, IFN-γ, IL-10 and IL-17 were measured. The results showed that polysaccharides from G. lucidum induced moderate to high amounts of innate inflammatory cytokines. Fungal cell-wall polysaccharides were stronger innate inflammatory cytokines inducers, while extracellular polysaccharides demonstrated a higher capacity to modulate cytokine responses of IONO+PMA induced production of IL-17. The results indicate that G. lucidum polysaccharides enhance Th1 response with high levels of IFN-γ and IL-2, and display low to no impact on IL-4 production. A similar pattern was observed at regulatory cytokine IL-10. All of the polysaccharide fractions tested induced IL-17 production at different concentration levels.

  1. An anti-interleukin-2 receptor drug attenuates T- helper 1 lymphocytes-mediated inflammation in an acute model of endotoxin-induced uveitis.

    Directory of Open Access Journals (Sweden)

    Salvador Mérida

    Full Text Available The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-γ, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60-70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFγ. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration.

  2. Oral supplementation of diabetic mice with propolis restores the proliferation capacity and chemotaxis of B and T lymphocytes towards CCL21 and CXCL12 by modulating the lipid profile, the pro-inflammatory cytokine levels and oxidative stress

    National Research Council Canada - National Science Library

    Al Ghamdi, Ahmad A; Badr, Gamal; Hozzein, Wael N; Allam, Ahmed; Al-Waili, Noori S; Al-Wadaan, Mohammed A; Garraud, Olivier

    2015-01-01

    .... To further elucidate the potential benefits of propolis, the present study investigated the effect of dietary supplementation with propolis on the plasma cytokine profiles, free radical levels, lipid...

  3. High mobility group box 1 protein (HMGB1) as an immune-modulating factor for polarization of human T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Lifeng Huang; Yongming Yao; Haidong Meng; Xiaodong Zhao; Ning Dong; Yan Yu

    2008-01-01

    Objective This study was performed to investigate the effect of high mobility group box-1 protein (HMGB 1) on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfunction.Methods Fresh blood was obtained from healthy adult volunteers and peripheral blood mononuclear cells (PBMCs) were isolated,then rhHMGB 1 was added to PBMCs.Four-color flow cytometric (FCM) analysis was used for the measurement of intracellular cytokine including interleukin Results (1) Different stimulating time and dosage of rhHMGB 1 did not alter the number of IFN-a positive cells (Th 1).rhHMGB 1 stimulation provoked a dose-dependent and time-dependent increase in Th2 subset and decrease in ratio of Th 1 to Th2.(2) Compared with the untreated cells,when the cells were coincubated with rhHMGB 1 (10-100ng/ml) for 12 hrs,protein release of IL-2 and sIL-2R were significantly up-regulated.At 48 hrs,in contrast,protein production was relatively lower in cells after exposure to 100-1000 ng/ml rhHMGBI.Conclusions These findings demonstrated that HMGB1 has a dual influence on immune functions of human T lymphocytes.

  4. Th1 and Th2 help for B cells

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1995-01-01

    Sustained interaction with Th1 cells has been shown to induce IL-2 responsiveness by murine B cells. This is equivalently dependent on CD40, CD54/ICAM-1 and MHC II ligation, and co-cross-linking of CD54 and MHC II in the presence of IL-5 up-regulates a functional IL-2R on B cells. We now show...... that IL-5 (125 U/ml) synergizes with Th1 cells to induce B cell responses to IL-2, that are maintained following T-cell removal, e.g. autonomous. Th1 help in the absence of IL-5 resulted in weak or undetectable responses following T cell removal. The mechanism of IL-5 synergy involved persistence of IL-2R...... beta expression following T cell removal, as opposed to enhancement of IL-2R induction or function. The level of contact-induced IL-2R expression on B cells was not itself modified by IL-5. The effects of IL-5 did not overcome the requirement for T contact signals and treatment of B cells with soluble...

  5. Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria

    Science.gov (United States)

    Lönnberg, Tapio; Svensson, Valentine; James, Kylie R.; Fernandez-Ruiz, Daniel; Sebina, Ismail; Montandon, Ruddy; Soon, Megan S. F.; Fogg, Lily G.; Nair, Arya Sheela; Liligeto, Urijah; Stubbington, Michael J. T.; Ly, Lam-Ha; Bagger, Frederik Otzen; Zwiessele, Max; Lawrence, Neil D.; Souza-Fonseca-Guimaraes, Fernando; Bunn, Patrick T.; Engwerda, Christian R.; Heath, William R.; Billker, Oliver; Stegle, Oliver; Haque, Ashraful; Teichmann, Sarah A.

    2017-01-01

    Differentiation of naïve CD4+ T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice. By tracking clonality using endogenous TCR sequences, we first demonstrated that Th1/Tfh bifurcation had occurred at both population and single-clone levels. Next, we identified genes whose expression was associated with Th1 or Tfh fates, and demonstrated a T-cell intrinsic role for Galectin-1 in supporting a Th1 differentiation. We also revealed the close molecular relationship between Th1 and IL-10-producing Tr1 cells in this infection. Th1 and Tfh fates emerged from a highly proliferative precursor that upregulated aerobic glycolysis and accelerated cell cycling as cytokine expression began. Dynamic gene expression of chemokine receptors around bifurcation predicted roles for cell-cell in driving Th1/Tfh fates. In particular, we found that precursor Th cells were coached towards a Th1 but not a Tfh fate by inflammatory monocytes. Thus, by integrating genomic and computational approaches, our study has provided two unique resources, a database www.PlasmoTH.org, which facilitates discovery of novel factors controlling Th1/Tfh fate commitment, and more generally, GPfates, a modelling framework for characterizing cell differentiation towards multiple fates. PMID:28345074

  6. Proteins of Leishmania (Viannia shawi confer protection associated with Th1 immune response and memory generation

    Directory of Open Access Journals (Sweden)

    Passero Luiz Felipe D

    2012-03-01

    Full Text Available Abstract Background Leishmania (Viannia shawi parasite was first characterized in 1989. Recently the protective effects of soluble leishmanial antigen (SLA from L. (V. shawi promastigotes were demonstrated using BALB/c mice, the susceptibility model for this parasite. In order to identify protective fractions, SLA was fractionated by reverse phase HPLC and five antigenic fractions were obtained. Methods F1 fraction was purified from L. (V. shawi parasite extract by reverse phase HPLC. BALB/c mice were immunized once a week for two consecutive weeks by subcutaneous routes in the rump, using 25 μg of F1. After 1 and 16 weeks of last immunization, groups were challenged in the footpad with L. (V. shawi promastigotes. After 2 months, those same mice were sacrificed and parasite burden, cellular and humoral immune responses were evaluated. Results The F1 fraction induced a high degree of protection associated with an increase in IFN-γ, a decrease in IL-4, increased cell proliferation and activation of CD8+T lymphocytes. Long-term protection was acquired in F1-immunized mice, associated with increased CD4+ central memory T lymphocytes and activation of both CD4+ and CD8+ T cells. In addition, F1-immunized groups showed an increase in IgG2a levels. Conclusions The inductor capability of antigens to generate memory lymphocytes that can proliferate and secrete beneficial cytokines upon infection could be an important factor in the development of vaccine candidates against American Tegumentary Leishmaniasis.

  7. Anesthesiology and the cytokine network

    Directory of Open Access Journals (Sweden)

    Barbara Lisowska

    2013-08-01

    Full Text Available The immune response is a highly specific reaction carried out by means of specialized cells that belong to the immune system. There are two types of immune response mechanisms aimed towards pathogens: non-specific, innate reactions, and specific, acquired reactions. Acquired immunity, characterized by its specificity, is comprised of lymphocytes, including both T cell and B cell populations. The role of B lymphocytes is not limited to the humoral response, though the cellular immune response is carried out mainly by various T lymphocyte subpopulations. The reactions of the humoral and cellular responses complement and stimulate one another mutually – cytokines are their common linking element. The attachment of cytokines to their specific receptors activates a sequence of signals – either intracellular or between the cells of various systems. This organization of respective connections and reactions, including the functional relations between cells of the immune response, in its complexity, is best described as a cytokine network. The response of the immune system to surgical trauma can be looked at from both a local and a general perspective. Not only surgical trauma caused by tissue damage, however, influences the functioning of the immune system, but also the drugs and techniques used during anesthesia. Our article is a presentation of the effects of medications used in anesthesia with respect to their influence on the cytokine network.

  8. IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures

    DEFF Research Database (Denmark)

    Blom, Lars; Poulsen, Lars K.

    2012-01-01

    The IL-1 family members IL-1ß, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood...... donors, and reactivated in the presence of IL-1ß, IL-18, or IL-33. Interestingly, we observe modifying responses in Th1 and Th2 cultures induced by IL-18 or IL-33 but not by IL-1ß, both contributing to amplify production of IL-5, IL-13, and IFN-¿. IL-18 or IL-33 stimulation of Th1 cultures resulted...... in increased IFN-¿ and IL-13 production concurrent with reduced IL-10 gene transcription and secretion even though Th1 cultures, in contrast to IL-18Ra, had low ST2L expression. Furthermore, adding IL-18 to Th1 cultures promoted Tbet mRNA expression and production. Th2 cultures stimulated with IL-18 or IL-33...

  9. 乳腺癌患者外周血Th1及Th2检测的临床意义%Clinical Significance of the Detection of Th1 and Th2 in Peripheral Blood of Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    彭利红; 高翠红; 肖凤艳; 潘慧芳

    2015-01-01

    【目的】探讨乳腺癌患者血清淋巴细胞亚群中辅助性 T 淋巴细胞1型/辅助性 T 淋巴细胞2型(T h1/T h2)的变化,为分析乳腺癌的发生发展和临床治疗提供免疫学指标。【方法】应用酶联免疫分析法(ELISA),测定46例乳腺癌患者和30例正常人组Th1型细胞因子[以白细胞介素‐2(IL‐2)、干扰素‐γ(INF‐γ)和肿瘤坏死因子‐α(T N F‐α)水平代表]和T h2型细胞因子[以白细胞介素‐4(IL‐4)、白细胞介素‐6(IL‐6)、白细胞介素‐8( IL‐8)、白细胞介素‐10( IL‐10)的水平代表]并将结果进行比较。【结果】乳腺癌患者 IL‐2、IN F‐γ的水平明显低正常对照组,且两组相比较差异有显著性( P <0.05);IL‐4、IL‐6、IL‐8、IL‐10、T N F‐α的水明显高于正常对照组,且两组相比较差异有显著性( P <0.05)。随着癌症分期的进展,乳腺癌患者血清IL‐2、IN F‐γ水平降低,T N F‐α、IL‐4、IL‐8、IL‐10水平升高,且差异均有显著性( P <0.05)。【结论】乳腺癌患者外周血呈现 T h1/T h2细胞因子失衡,其中 T h1亚群功能抑制,T h2亚群功能亢进,其与肿瘤在宿主体内生长密切相关,通过纠正这些免疫失调将成为乳腺癌治疗的重要手段。%Objective] To explore the changes of T‐lymphocyte helper 1/2(Th1/Th2) of lymphocyte sub‐sets in serum of patients with breast cancer in order to provide immunological indexes for the analysis of occur‐rence and development and clinical treatment .[Methods] Enzyme linked immunosorbent assay(ELISA) was used to detect serum levels of Th1‐type cytokines(IL‐2 ,INF‐γand TNF‐α) and Th2‐type cytokines(IL‐4 ,IL‐6 ,IL‐8 and IL‐10) in 45 patients with breast cancer and 30 normal subjects .The results were compared .[Re‐sults] The levels of IL‐2 and INF‐γin breast cancer group were obviously

  10. Do Helper T Cell Subtypes in Lymphocytic Thyroiditis Play a Role in the Antitumor Effect?

    Science.gov (United States)

    Yang, Seok Woo; Kang, Seong-Ho; Kim, Kyung Rae; Choi, In Hong; Chang, Hang Seok; Oh, Young Lyun; Hong, Soon Won

    2016-01-01

    Background Papillary thyroid carcinoma (PTC) is frequently accompanied by lymphocytic thyroiditis (LT). Some reports claim that Hashimoto’s thyroiditis (the clinical form of LT) enhances the likelihood of PTC; however, others suggest that LT has antitumor activity. This study was aimed to find out the relationship between the patterns of helper T cell (Th) cytokines in thyroid tissue of PTC with or without LT and the clinicopathological manifestation of PTC. Methods Fresh surgical samples of PTC with (13 cases) or without (10 cases) LT were used. The prognostic parameters (tumor size, extra-thyroidal extension of PTC, and lymph node metastasis) were analyzed. The mRNA levels of two subtypes of Th cytokines, Th1 (tumor necrosis factor α [TNF-α], interferon γ [IFN-γ ], and interleukin [IL] 2) and Th2 (IL-4 and IL-10), were analyzed. Because most PTC cases were microcarcinomas and recent cases without clinical follow-up, negative or faint p27 immunoreactivity was used as a surrogate marker for lymph node metastasis. Results PTC with LT cases showed significantly higher expression of TNF-α (p = .043), IFN-γ (p < .010), IL-4 (p = .015) than those without LT cases. Although the data were not statistically significant, all analyzed cytokines (except for IL-4) were highly expressed in the cases with higher expression of p27 surrogate marker. Conclusions These results indicate that mixed Th1 (TNF-α, IFN-γ , and IL-2) and Th2 (IL-10) immunity might play a role in the antitumor effect in terms of lymph node metastasis. PMID:27681413

  11. Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist.

    Science.gov (United States)

    Krieg, Arthur M; Efler, Susan M; Wittpoth, Michael; Al Adhami, Mohammed J; Davis, Heather L

    2004-01-01

    Subcutaneous injection of normal human volunteers with a B-class CpG oligodeoxynucleotide (ODN) TLR9 agonist, CPG 7909, induced a TH1-like pattern of systemic innate immune activation manifested by expression of IL-6, IL-12p40, IFN-alpha, and IFN-inducible chemokines. Serum IP-10 was found to be the most sensitive assay for subcutaneous CPG 7909 stimulation; its level was significantly increased in all subjects at all dose levels, including the lowest tested dose of just 0.0025 mg/kg. This pattern of chemokine and cytokine induction was markedly different from that previously reported to be induced by TLR9 stimulation in rodents, most likely reflecting species-specific differences in the cell types expressing TLR9. Subcutaneous CPG 7909 injection induced transient shifts in blood neutrophils, lymphocytes, and monocytes, consistent with the increased chemokine expression. Levels of acute phase reactants such as C-reactive protein were also increased. A second subcutaneous CPG 7909 injection administered 2 weeks after the first elicited similar immune responses, showing little or no tolerance to the effects of repeated in vivo TLR9 stimulation. Subjects developed dose-dependent transient injection site reactions and flu-like symptoms but otherwise tolerated injection well, with no evidence of organ toxicity or systemic autoimmunity. The activation of innate immunity was dependent on the route of ODN administration, since intravenous injection caused no such effects. These studies indicate that in vivo activation of TLR9 by subcutaneous administration of CPG 7909 could be a well-tolerated immunotherapeutic approach for induction of TH1 innate immune activation.

  12. Fatigue favors in vitro Th1 and Th17-like cell expansion and reduces corticoid sensitivity in MS patients.

    Science.gov (United States)

    Alvarenga-Filho, Hélcio; Salles, Marisa; Hygino, Joana; Ferreira, Thais B; Sacramento, Priscila M; Monteiro, Clarice; Vasconcelos, Claudia Cristina F; Alvarenga, Regina Maria Papais; Bento, Cleonice A M

    2017-02-15

    Fatigue is a common "ghost" symptom in patients with multiple sclerosis (MS), an autoimmune disease mediated by T cells that target myelin antigens of the central nervous system. As fatigue has been associated with inflammatory states, its occurrence may negatively impact MS progression. The aim of this study was to evaluate the impact of fatigue on the cytokine profile of patients with relapsing-remitting (RR) MS. For our study, blood were collected from MS patients in clinical remission phase with (n=15) and without (n=15) fatigue. Cytokines were detected by ELISA in the plasma and supernatant collected from anti-CD3/anti-CD28-activated T cells or LPS-stimulated monocytes. In some wells, different doses of hydrocortisone (HC) were added at the beginning of the culture. Here, peripheral levels of IL-6 and TNF-α, as well as in vitro production of cytokines related to Th17 (IL-6, IL-17, IL-22, and GM-CSF) or Th1 (IFN-γ) phenotypes, were elevated in fatigued patients and their levels were associated with fatigue severity. The same phenomenon was observed between the production of IL-6, TNF-α, IL-1β, and IL-23 by monocytes and fatigue. Moreover, HC was less efficient in inhibiting in vitro inflammatory cytokine production in patients with fatigue, mainly those produced by both CD8(+) T cells and monocytes. Our data, although preliminary, suggests that the occurrence of fatigue, by favoring the in vitro production of Th1/Th17-related cytokines and corticoid resistance, may negatively impact the course of MS.

  13. The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major

    DEFF Research Database (Denmark)

    Kemp, M; Handman, E; Kemp, K

    1998-01-01

    . Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-gamma and tumour necrosis factor...... and that these cells were the major source of interferon-gamma. The results show that Th1-like cells recognising PSA-2 are expanded during infection by L. major and that they maintain their Th1-like cytokine profile upon reactivation in vitro. Since immunity to cutaneous leishmaniasis is mediated by antigen...

  14. [Immunomodulation of Uncaria tomentosa over dendritic cells, il-12 and profile TH1/TH2/TH17 in breast cancer].

    Science.gov (United States)

    Núñez, César; Lozada-Requena, Iván; Ysmodes, Tíndara; Zegarra, Daniel; Saldaña, Fatima; Aguilar, José

    2015-10-01

    Objetives. This study aimed to research the in vitro immunomodulatory effects of an Uncaria tomentosa hydroalcoholic extract standardized (5.03%, pentacyclic oxindole alkaloids) (UT-POA) on the immunophenotype of dendritic cells (DC) subsets, Th1, Th2, Th17 and IL-12 cytokines from patients with stage II breast cancer (BCII) and healthy women (H). Blood of 11 H and 7 BCII was obtained, PBMC were isolated and cultured for 2h with/without various concentrations of UT-POA and stimulated or not with LPS for 24h. PBMC were labeled with specific antibodies for DC and in the supernatant we measured Th1/Th2/Th17 cytokines, both by flow cytometry. Furthermore IL-12 was measured by ELISA. UT-POA did not alter DC or accessory molecules expression in BCII. However, H exhibited a decrease in the percentage of mDC (myeloid DC) and an increase in HLA-DR and CD86 expression at 1000 μg/mL. IL-12 secretion was modified only in the H group, increasing p70 subunit and decreasing p40 subunit. UT-POA increased Th1 (IFN-γ and IL-2), Th2 (IL-4) and Th17 (IL-17) secretion in both groups. UT-POA increased the production of cytokines related with anti-tumoral response at concentrations of 500-1000 μg/mL. This positive effect should be evaluated not only systemically but also in the tumor microenvironment in further studies. UT-POA may be a useful phytochemical in chemoprevention and in the alternative use in cancer therapies.

  15. CD4(+) memory T cells with high CD26 surface expression are enriched for Th1 markers and correlate with clinical severity of multiple sclerosis

    DEFF Research Database (Denmark)

    Krakauer, M; Sorensen, P S; Sellebjerg, F

    2006-01-01

    An aberrant immune activation is believed to be important in the pathogenesis of multiple sclerosis (MS). Expression of CD4(+) T lymphocyte surface molecules indicative of immune activation and effector functions has been correlated with disease severity and activity. CD4(+) CD45R0(+) CD26(high......) memory T lymphocytes contained the high levels of markers of Th1, activation, and effector functions and cell counts of this subset correlated with MS disease severity. This subset had lower expression of PD-1, CCR4, and L-selectin in MS than in controls. These changes were only partially normalised...

  16. Prevalence of atopy in children with type 1 diabetes mellitus, hepatitis B virus carriers, and healthy children: role of T helper 1 (Th1)-type immune response.

    Science.gov (United States)

    Cakir, Murat; Akcay, Seker; Karakas, Taner; Gedik, Yusuf; Okten, Aysenur; Orhan, Fazil

    2008-01-01

    The prevalence of allergic diseases such as asthma, hay fever, and atopic dermatitis has increased over the past few decades, especially in developed countries. They are characterized by a chronic inflammatory reaction mediated by T helper 2 (Th2) cells. Two common chronic diseases of childhood-an autoimmune disease, type 1 diabetes mellitus (DM), and a chronic viral infection, hepatitis B virus (HBV) carriers-are associated with a Th1-dominant and Th1-insufficient cytokine profile, respectively. The purpose of this study was to analyze the frequency of allergic disease in patients with type 1 DM and, in HBV carriers, to evaluate the role of Th1-type immune response in atopy and allergic disease. The study included patients with type 1 DM (group I, n = 52), HBV carriers (group III, n = 47), and a healthy control group (group III, n = 209). Participants were screened for allergic disease and atopic sensitization. Symptoms of asthma, eczema, and atopy were found more commonly in HBV carrier children compared with those with DM and healthy controls. This study supports the Th1/Th2 model. The prevalence of allergic disease and atopy is decreased in Th1-mediated autoimmune disease, type 1 DM, and, conversely, is increased in insufficient Th1 response, chronic HBV carriers. Additional studies are needed to evaluate the effect of atopy and allergic diseases in glycemic control and long-term complications in patients with type 1 DM and the effect of atopy on progression of chronic HBV infection.

  17. CD30 antigen: not a physiological marker for TH2 cells but an important costimulator molecule in the regulation of the balance between TH1/TH2 response.

    Science.gov (United States)

    Pellegrini, Patrizia; Berghella, Anna Maria; Contasta, Ida; Adorno, Domenico

    2003-01-01

    Understanding the physiological role of CD30 would be an important step forward in transplants because CD30+ T cells can be induced by alloantigens even in the presence of immunosuppressives such as cyclosporine (Csa) and hence can act as regulatory cells in allograft. The results of functional studies on purified T CD30+ cell populations led us to hypothesize that the CD30 costimulator molecule is not a specific marker for TH2 cells in normal conditions, as has been suggested, but rather a marker for an important immunoregulatory subpopulation that regulates the balance between TH1 and TH2 (TH1/TH2) type response. To substantiate this hypothesis we studied the TH1/TH2 cytokine network in peripheral whole blood cultures stimulate with M44 CD30 ligand (CD30L), an agonistic monoclonal antibody (mAb). Four types of whole blood culture were used: the first had been stimulated with anti-CD3 mAb which generates a CD30 cytokine profile similar to alloreactive stimulation; the second with anti-CD3 mAb+M81 (an anti-CD30L mAb) to inhibit CD30/CD30L interaction; the third with anti-CD3+anti-interleukin (IL)4 mAbs to counteract IL4 activity and the fourth with anti-CD3+anti-interferon (IFN)gamma mAbs to counteract IFNgamma activity. Network interactions between soluble CD30 (sCD30, a maker of CD30 expression), sBcl2 (a marker of cell survival) and TH1/TH2 cytokines (IFNgamma, IL2, IL12p70, IL12p40, IL4, IL5 and IL10) were then studied in the supernatants obtained. Our results confirm the hypothesis above by showing that CD30 signals trigger functional mechanisms responsible for changes in levels of production of several important TH1 and TH2 cytokines involved in the regulation of the physiological balance between TH1/TH2 functions. The CD30-stimulated network, in fact, induces IFNgamma production linked to TH1 activity (-->TH1) which is subsequently integrated by IL4 production linked to TH2 activity (-->TH2). This production appears to be regulated, respectively, by IL12p40

  18. Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils.

    Science.gov (United States)

    Al-Muhsen, Saleh; Letuve, Severine; Vazquez-Tello, Alejandro; Pureza, Mary Angeline; Al-Jahdali, Hamdan; Bahammam, Ahmed S; Hamid, Qutayba; Halwani, Rabih

    2013-03-13

    Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood. In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines. Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays. The basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release. Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.

  19. Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Chen-Chen Lee

    2015-01-01

    Full Text Available This study investigated the immunomodulatory effects of ferulic acid (FA on antigen-presenting dendritic cells (DCs in vitro and its antiallergic effects against ovalbumin- (OVA- induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS stimulation induced a high level of interleukin- (IL- 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF- α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4, MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13, and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN- γ production in bronchoalveolar lavage fluid (BALF and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

  20. CD4+ Th17 cells discriminate clinical types and constitute a third subset of non Th1, Non Th2 T cells in human leprosy.

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    Chaman Saini

    Full Text Available BACKGROUND: Patients with localized tuberculoid and generalized lepromatous leprosy show respectively Th1 and Th2 cytokine profile. Additionally, other patients in both types of leprosy also show a non discriminating Th0 cytokine profile with both interferon-γ and IL-4. The present study investigated the role of Th17 cells which appear to be a distinct subtype of Th subtypes in 19 tuberculoid and 18 lepromatous leprosy patients. Five healthy subjects with long term exposure to infection and 4 skin biopsies from healthy subjects undergoing cosmetic surgery were used as controls. METHODOLOGY/PRINCIPLE FINDINGS: An array of Th17 related primers for cytokines, chemokines and transcription factors was used in real time reverse transcribed PCR to evaluate gene expression, ELISA for cytokine secretion in the supernatants of antigen stimulated PBMC cultures and flow cytometry for establishing the phenotype of the IL-17, IL-21 producing cells. CONCLUSIONS/SIGNIFICANCE: IL-17 isoforms showed significantly higher expression and release in supernatants of antigen stimulated PBMC cultures and dermal lesions of healthy contacts and tuberculoid leprosy as compared to lepromatous leprosy (p<0.003. This was further confirmed by Th17 associated transcription factor RORC, cytokines IL-21, IL-22, and IL-23, chemokines MMP13, CCL20, CCL22. Of interest was the association of IL-23R and not IL-6R with IL-17(+ cells. The Th17 cells were CD4(+ CCR6(+ confirming their effector cell lineage. Polarized Th1 cytokines were seen in 3/7 tuberculoid and Th2 cytokines in 5/10 lepromatous leprosy patients. Of importance was the higher association of Th17 pathway factors with the non-polarized Th0 types as compared to the polarized Th1 and Th2 (p<0.01. Our study draws attention to a third type of effector Th cell that may play a role in leprosy.

  1. CD4+ Th17 Cells Discriminate Clinical Types and Constitute a Third Subset of Non Th1, Non Th2 T Cells in Human Leprosy

    Science.gov (United States)

    Saini, Chaman; Ramesh, V.; Nath, Indira

    2013-01-01

    Background Patients with localized tuberculoid and generalized lepromatous leprosy show respectively Th1 and Th2 cytokine profile. Additionally, other patients in both types of leprosy also show a non discriminating Th0 cytokine profile with both interferon-γ and IL-4. The present study investigated the role of Th17 cells which appear to be a distinct subtype of Th subtypes in 19 tuberculoid and 18 lepromatous leprosy patients. Five healthy subjects with long term exposure to infection and 4 skin biopsies from healthy subjects undergoing cosmetic surgery were used as controls. Methodology/Principle Findings An array of Th17 related primers for cytokines, chemokines and transcription factors was used in real time reverse transcribed PCR to evaluate gene expression, ELISA for cytokine secretion in the supernatants of antigen stimulated PBMC cultures and flow cytometry for establishing the phenotype of the IL-17, IL-21 producing cells. Conclusions/Significance IL-17 isoforms showed significantly higher expression and release in supernatants of antigen stimulated PBMC cultures and dermal lesions of healthy contacts and tuberculoid leprosy as compared to lepromatous leprosy (p<0.003). This was further confirmed by Th17 associated transcription factor RORC, cytokines IL-21, IL-22, and IL-23, chemokines MMP13, CCL20, CCL22. Of interest was the association of IL-23R and not IL-6R with IL-17+ cells. The Th17 cells were CD4+ CCR6+ confirming their effector cell lineage. Polarized Th1 cytokines were seen in 3/7 tuberculoid and Th2 cytokines in 5/10 lepromatous leprosy patients. Of importance was the higher association of Th17 pathway factors with the non-polarized Th0 types as compared to the polarized Th1 and Th2 (p<0.01). Our study draws attention to a third type of effector Th cell that may play a role in leprosy. PMID:23936569

  2. Chemokine receptor CCR7 regulates the intestinal TH1/TH17/Treg balance during Crohn's-like murine ileitis.

    Science.gov (United States)

    McNamee, Eóin N; Masterson, Joanne C; Veny, Marisol; Collins, Colm B; Jedlicka, Paul; Byrne, Fergus R; Ng, Gordon Y; Rivera-Nieves, Jesús

    2015-06-01

    The regulation of T cell and DC retention and lymphatic egress within and from the intestine is critical for intestinal immunosurveillance; however, the cellular processes that orchestrate this balance during IBD remain poorly defined. With the use of a mouse model of TNF-driven Crohn's-like ileitis (TNF(Δ) (ARE)), we examined the role of CCR7 in the control of intestinal T cell and DC retention/egress during experimental CD. We observed that the frequency of CCR7-expressing TH1/TH17 effector lymphocytes increased during active disease in TNF(Δ) (ARE) mice and that ΔARE/CCR7(-/-) mice developed exacerbated ileitis and multiorgan inflammation, with a marked polarization and ileal retention of TH1 effector CD4(+) T cells. Furthermore, adoptive transfer of ΔARE/CCR7(-/-) effector CD4(+) into lymphopenic hosts resulted in ileo-colitis, whereas those transferred with ΔARE/CCR7(+/+) CD4(+) T cells developed ileitis. ΔARE/CCR7(-/-) mice had an acellular draining MLN, decreased CD103(+) DC, and decreased expression of RALDH enzymes and of CD4(+)CD25(+)FoxP3(+) Tregs. Lastly, a mAb against CCR7 exacerbated ileitis in TNF(Δ) (ARE) mice, phenocopying the effects of congenital CCR7 deficiency. Our data underscore a critical role for the lymphoid chemokine receptor CCR7 in orchestrating immune cell traffic and TH1 versus TH17 bias during chronic murine ileitis.

  3. mTOR regulates TLR-induced c-fos and Th1 responses to HBV and HCV vaccines

    Institute of Scientific and Technical Information of China (English)

    Li; He; Aiping; Zang; Min; Du; Dapeng; Ma; Chuanping; Yuan; Chun; Zhou; Jing; Mu; Huanjing; Shi; Dapeng; Li; Xulin; Huang; Qiang; Deng; Jianhua; Xiao; Huimin; Yan; Lijian; Hui; Ke; Lan; Sidong; Xiong; Xiaoxia; Li; Zhong; Huang; Hui; Xiao

    2015-01-01

    Although IL-12 plays a critical role in priming Th1 and cytotoxic T lymphocyte(CTL) responses, Toll-like receptor(TLR) signaling only induces low amounts of IL-12 in dendritic cells and macrophages, implying the existence of stringent regulatory mechanisms. In this study, we sought to uncover the mechanisms underlying TLR-induced IL-12 expression and the Th1 response. By systemic screening, we identified a number of protein kinases involved in the regulation of TLRinduced IL-12 expression. In particular, PI3 K, ERK, and m TOR play critical roles in the TLR-induced Th1 response by regulating IL-12 and IL-10 production in innate immune cells. Moreover, we identified c-fos as a key molecule that mediates m TOR-regulated IL-12 and IL-10 expression in TLR signaling. Mechanistically, m TOR plays a crucial role in c-fos expression, thereby modulating NFκB binding to promoters of IL-12 and IL-10. By controlling the expression of a special innate gene program, m TOR can specifically regulate the TLR-induced T cell response in vivo. Furthermore, blockade of m TOR by rapamycin efficiently boosted TLR-induced antigen-specific T and B cell responses to HBV and HCV vaccines. Taken together, these results reveal a novel mechanism through which m TOR regulates TLR-induced IL-12 and IL-10 production, contributing new insights for strategies to improve vaccine efficacy.

  4. Cytokines and Immune Responses in Murine Atherosclerosis.

    Science.gov (United States)

    Kusters, Pascal J H; Lutgens, Esther

    2015-01-01

    Atherosclerosis is an inflammatory disease of the vessel wall characterized by activation of the innate immune system, with macrophages as the main players, as well as the adaptive immune system, characterized by a Th1-dominant immune response. Cytokines play a major role in the initiation and regulation of inflammation. In recent years, many studies have investigated the role of these molecules in experimental models of atherosclerosis. While some cytokines such as TNF or IFNγ clearly had atherogenic effects, others such as IL-10 were found to be atheroprotective. However, studies investigating the different cytokines in experimental atherosclerosis revealed that the cytokine system is complex with both disease stage-dependent and site-specific effects. In this review, we strive to provide an overview of the main cytokines involved in atherosclerosis and to shed light on their individual role during atherogenesis.

  5. Cytokine Profiles in Adult Mink Infected with Aleutian Mink Disease Parvovirus

    Science.gov (United States)

    Jensen, P. V.; Castelruiz, Y.; Aasted, B.

    2003-01-01

    The aim of this study was to examine the levels of gamma interferon (IFN-γ)-, interleukin 4 (IL-4)-, and IL-8-producing cells in peripheral blood mononuclear cells from mink infected with the Aleutian mink disease parvovirus (ADV). As expected, ADV-infected mink developed high plasma gamma globulin values (hypergammaglobulinemia) and enhanced quantities of CD8-positive (CD8+) cells in the blood during the infection. We quantified the percentages of IFN-γ- and IL-4-positive lymphocytes and IL-8-positive monocytes up to week 38 after virus challenge. The results clearly indicated marked increases in the percentages of IFN-γ- and IL-4-producing lymphocytes during ADV infection. The total number of IL-8-producing monocytes in the blood of ADV-infected mink stayed fairly constant during the infection. In order to characterize the phenotype of the cytokine-producing cells, we performed double-labeling fluorescence-activated cell sorter (FACS) experiments with CD8 surface labeling in one channel and cytokine intracellular staining in the other. We found that most IFN-γ and IL-4 in ADV-infected mink was produced by CD8+ cells, while in the uninfected mink, these cytokines were primarily produced by a cell type that was not CD8 (possibly CD4-positive cells). We also observed that IL-8 was almost exclusively produced by monocytes. All of the above findings led us to conclude that both Th1- and Th2-driven immune functions are found in mink plasmacytosis. PMID:12805443

  6. 银屑病中免疫细胞和细胞因子的作用%The role of immunocytes and cytokines in psoriasis

    Institute of Scientific and Technical Information of China (English)

    颜克香; 黄琼; 郑志忠

    2008-01-01

    Psoriasis is an autoimmune disease that is associated with T lymphocytes. Recent research has shown that besides Th1 cells, Th17 cells and related cytokines play a very important role in the pathogenesis of psoriasis. The differentiation and activation of T lymphocytes requires the participation of antigen-presenting cells. Cytokines released by activated mast cells also take part in the pathogenesis of psoriasis. Therefore, a great many of immunocytes and cytokines are involved in the development of psoriasis. To elucidate the immunologic mechanism in the pathogenesis of psoriasis may provide theoretic evidence for the development of new approaches to psoriasis treatment.%银屑病是一种与T淋巴细胞相关的自身免疫性疾病,新近研究发现除与Th1细胞有关外,Th17细胞及其相关的细胞因子在银屑病发病中也起重要的作用.T淋巴细胞的活化和分化需要抗原提呈细胞参与,肥大细胞活化后释放的细胞因子也参与银屑病发病.因此,银屑病是由多种免疫细胞和细胞因子共同参与的疾病.阐明银屑病发病的免疫机制可为银屑病治疗开辟新疗法提供理论依据.

  7. Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α

    Directory of Open Access Journals (Sweden)

    Márcia Antoniazi Michelin

    2015-03-01

    Full Text Available Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+ lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN. We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern.

  8. The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production.

    Science.gov (United States)

    Jensen, Kristoffer Jarlov; Fisker, Ane Bærent; Andersen, Andreas; Sartono, Erliyani; Yazdanbakhsh, Maria; Aaby, Peter; Erikstrup, Christian; Benn, Christine Stabell

    2016-02-28

    As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP ≥ 5 mg/l (28 v. 12%; P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γ responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95% CI 1·44, 10·90) but not in males (GMR 0·44; 95% CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS.

  9. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.

    Directory of Open Access Journals (Sweden)

    Joseph N Jarvis

    2015-04-01

    Full Text Available Understanding the host immune response during cryptococcal meningitis (CM is of critical importance for the development of immunomodulatory therapies. We profiled the cerebrospinal fluid (CSF immune-response in ninety patients with HIV-associated CM, and examined associations between immune phenotype and clinical outcome. CSF cytokine, chemokine, and macrophage activation marker concentrations were assayed at disease presentation, and associations between these parameters and microbiological and clinical outcomes were examined using principal component analysis (PCA. PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines. The presence of this CSF cytokine response was associated with evidence of increased macrophage activation, more rapid clearance of Cryptococci from CSF, and survival at 2 weeks. The key components of this protective immune-response were interleukin (IL-6 and interferon-γ, IL-4, IL-10 and IL-17 levels also made a modest positive contribution to the PC1 score. A second component of co-correlated chemokines was identified by PCA, consisting primarily of monocyte chemotactic protein-1 (MCP-1 and macrophage inflammatory protein-1α (MIP-1α. High CSF chemokine concentrations were associated with low peripheral CD4 cell counts and CSF lymphocyte counts and were predictive of immune reconstitution inflammatory syndrome (IRIS. In conclusion CSF cytokine and chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM. We speculate that the presence of even minimal Cryptococcus-specific Th1-type CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes and monocytes into the central nervous system (CNS, more effective activation of CNS macrophages and microglial cells, and faster organism clearance; while high CNS chemokine levels may predispose to over recruitment or inappropriate recruitment of immune cells to the CNS and

  10. Study of Th1/Th2 balance in peripheral blood mononuclear cells of patients with alopecia areata.

    Science.gov (United States)

    Sadeghi, Soha; Sanati, Mohammad Hossein; Taghizadeh, Morteza; Mansouri, Parvine; Jadali, Zohreh

    2015-09-01

    Alopecia areata represents an autoimmune pathological process driven primarily by cellular aberrations contained within the immune system, which activates various humoral and cellular elements of the immune response. The aim of this study was to determine the mRNA expression levels of T-bet and GATA-3 as potential inducers of T helper (Th)1 and Th2 differentiation, respectively, as well as Th1(IFN-γ) and Th2(IL-4) cytokine mRNA expression in patients with alopecia areata. Using real-time reverse transcriptase PCR (RT-PCR), the relative amounts of T-bet, GATA-3, IFN-γ, and IL-4 mRNA transcripts were determined in PBMCs from 20 Iranian patients with alopecia areata and compared with those of 20 healthy control subjects. In comparison with the normal group, T-bet and IFN-γ mRNA expression levels were significantly up-regulated in the alopecia areata patients, while GATA-3 and IL-4 mRNA expression levels were down-regulated. Notably, positive correlation (P < 0.05) was found between IFN-γ and T-bet levels in patients and controls. In addition, significant positive correlations existed between GATA-3 and IL-4 (P < 0.05). These results indicate that a Th1/Th2 imbalance exists in alopecia areata, and it may be implicated in the pathogenesis of disease.

  11. D-pinitol regulates Th1/Th2 balance via suppressing Th2 immune response in ovalbumin-induced asthma.

    Science.gov (United States)

    Lee, Jun Sik; Lee, Chang-Min; Jeong, Young-Il; Jung, In Duk; Kim, Bo-Hye; Seong, Eun-Young; Kim, Jong-Il; Choi, Il-Whan; Chung, Hae Young; Park, Yeong-Min

    2007-01-09

    D-pinitol has been demonstrated to exert insulin-like and anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. Recently, it was shown that T-bet and GATA-3 are master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether D-pinitol regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in OVA-induced asthma model mice. We also examined to ascertain whether D-pinitol could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of D-pinitol before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that D-pinitol plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of D-pinitol in terms of its effects in a murine model of asthma, and also broaden current perspectives in our understanding of the immunopharmacological functions of D-pinitol.

  12. Pathogenesis of Renal Disease in Systemic Lupus Erythematosus—The Role of Autoantibodies and Lymphocytes Subset Abnormalities

    Directory of Open Access Journals (Sweden)

    Desmond Y. H. Yap

    2015-04-01

    Full Text Available Lupus nephritis (LN is a common and severe organ manifestation of systemic lupus erythematosus (SLE, and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of SLE and LN, and might reflect disease activity and are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied autoantibodies, which correlates with disease activity and has direct nephritogenic effects on resident renal cells and various glomerular components. Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti-α-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells and plasma cells have been observed in SLE and LN patients. These B cell subsets exert diverse effects during pathogenesis of LN such as production of autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and presentation of auto-antigens to effector cells. Aberration of T lymphocytes, especially the T-helper subsets, is also highly pertinent in the development of LN. In this context, important T helper subsets include Th1, Th2, Th9, Th17, TReg and follicular T-helper cells. The growing knowledge on these autoantibodies and lymphocyte subset abnormalities will enhance our understanding of SLE and LN, and hence help devise better strategies for disease monitoring and treatment.

  13. Th2/1 Hybrid Cells Occurring in Murine and Human Strongyloidiasis Share Effector Functions of Th1 Cells

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    Cristin N. Bock

    2017-06-01

    Full Text Available Infections by the soil-transmitted threadworm Strongyloides stercoralis affect 30–100 million people worldwide, predominantly in tropic and sub-tropic regions. Here we assessed the T helper cell phenotypes in threadworm-infected patients and experimental murine infections with focus on CD4+ T cells co-expressing markers of Th2 and Th1 differentiation. We show that mice infected with the close relative S. ratti generate strong Th2 responses characterized by the expansion of CD4+ GATA-3+ cells expressing IL-4/-5/-13 in blood, spleen, gut-draining lymph nodes, lung and gut tissue. In addition to conventional Th2 cells, significantly increased frequencies of GATA-3+T-bet+ Th2/1-hybrid cells were detected in all organs and co-expressed Th2- and Th1-cytokines at intermediate levels. Assessing the phenotype of blood-derived CD4+ T cells from South Indian patients infected with S. stercoralis and local uninfected control donors we found that GATA-3 expressing Th2 cells were significantly increased in the patient cohort, coinciding with elevated eosinophil and IgE/IgG4 levels. A fraction of IL-4+CD4+ T cells simultaneously expressed IFN-γ hence displaying a Th2/1 hybrid phenotype. In accordance with murine Th2/1 cells, human Th2/1 cells expressed intermediate levels of Th2 cytokines. Contrasting their murine counterparts, human Th2/1 hybrids were marked by high levels of IFN-γ and rather low GATA-3 expression. Assessing the effector function of murine Th2/1 cells in vitro we found that Th2/1 cells were qualified for driving the classical activation of macrophages. Furthermore, Th2/1 cells shared innate, cytokine-driven effector functions with Th1 cells. Hence, the key findings of our study are that T helper cells with combined characteristics of Th2 and Th1 cells are integral to immune responses of helminth-infected mice, but also occur in helminth-infected humans and we suggest that Th2/1 cells are poised for the instruction of balanced immune

  14. The CC-chemokine receptor 5 (CCR5) is a marker of, but not essential for the development of human Th1 cells

    DEFF Research Database (Denmark)

    Odum, Niels; Bregenholt, S; Eriksen, K W

    1999-01-01

    The CC-chemokine receptor 5 (CCR5) has recently been described as a surface marker of human T cells producing type 1 (Th1) cytokines. Here we confirm that CCR5 is expressed on human Th1 but not on Th2 T-cell clones. Using intracellular cytokine staining, we show that alloantigen specific CD4+ T......-cell lines derived from a CCR5-deficient individual (delta32 allele homozygote) contain high numbers of both interferon gamma (IFN-gamma) and interleukin (IL)-2 producing cells, low numbers of IL-10 producing cells and no IL4 or IL-5 producing cells when stimulated with phorbol ester and ionomycin in vitro...

  15. Levamisole promotes murine bone marrow derived dendritic cell activation and drives Th1 immune response in vitro and in vivo.

    Science.gov (United States)

    Fu, Yubing; Wang, Ting; Xiu, Lei; Shi, Xiaojie; Bian, Ziyao; Zhang, Yongli; Ruhan, A; Wang, Xiao

    2016-02-01

    Our lab previously found that levamisole (LMS) as an adjuvant enhanced the efficacy of vaccine against infectious pathogens. However, the cellular and molecular mechanisms remain to be defined. In this study, we showed that BALB/c bone marrow-derived DC stimulated with LMS resulted in enhanced cell-surface expression of CD80, CD86, CD40 and MHC class II, as well as enhanced production of IL-12p70, TNF-α and IL-1β. Interestingly, the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction. Furthermore, to confirm the in vitro data, we investigated the effect of LMS on antigen-specific antibody and cytokine production in BALB/c mice. Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were increased significantly compared with OVA alone in BALB/c mice. In conclusion, our results suggested that murine bone marrow-derived DC, played a crucial role in the effect of LMS on the induction of Th1 responses, which probably was due to its ability to promote DC maturation and secrete proinflammatory cytokines.

  16. Neutrophils Exert a Suppressive Effect on Th1 Responses to Intracellular Pathogen Brucella abortus

    Science.gov (United States)

    Ordoñez-Rueda, Diana; Arce-Gorvel, Vilma; Alfaro-Alarcón, Alejandro; Lepidi, Hubert; Malissen, Bernard; Malissen, Marie; Gorvel, Jean-Pierre; Moreno, Edgardo

    2013-01-01

    Polymorphonuclear neutrophils (PMNs) are the first line of defense against microbial pathogens. In addition to their role in innate immunity, PMNs may also regulate events related to adaptive immunity. To investigate the influence of PMNs in the immune response during chronic bacterial infections, we explored the course of brucellosis in antibody PMN-depleted C57BL/6 mice and in neutropenic mutant Genista mouse model. We demonstrate that at later times of infection, Brucella abortus is killed more efficiently in the absence of PMNs than in their presence. The higher bacterial removal was concomitant to the: i) comparatively reduced spleen swelling; ii) augmented infiltration of epithelioid histiocytes corresponding to macrophages/dendritic cells (DCs); iii) higher recruitment of monocytes and monocyte/DCs phenotype; iv) significant activation of B and T lymphocytes, and v) increased levels of INF-γ and negligible levels of IL4 indicating a balance of Th1 over Th2 response. These results reveal that PMNs have an unexpected influence in dampening the immune response against intracellular Brucella infection and strengthen the notion that PMNs actively participate in regulatory circuits shaping both innate and adaptive immunity. PMID:23458832

  17. Neutrophils exert a suppressive effect on Th1 responses to intracellular pathogen Brucella abortus.

    Directory of Open Access Journals (Sweden)

    Elías Barquero-Calvo

    2013-02-01

    Full Text Available Polymorphonuclear neutrophils (PMNs are the first line of defense against microbial pathogens. In addition to their role in innate immunity, PMNs may also regulate events related to adaptive immunity. To investigate the influence of PMNs in the immune response during chronic bacterial infections, we explored the course of brucellosis in antibody PMN-depleted C57BL/6 mice and in neutropenic mutant Genista mouse model. We demonstrate that at later times of infection, Brucella abortus is killed more efficiently in the absence of PMNs than in their presence. The higher bacterial removal was concomitant to the: i comparatively reduced spleen swelling; ii augmented infiltration of epithelioid histiocytes corresponding to macrophages/dendritic cells (DCs; iii higher recruitment of monocytes and monocyte/DCs phenotype; iv significant activation of B and T lymphocytes, and v increased levels of INF-γ and negligible levels of IL4 indicating a balance of Th1 over Th2 response. These results reveal that PMNs have an unexpected influence in dampening the immune response against intracellular Brucella infection and strengthen the notion that PMNs actively participate in regulatory circuits shaping both innate and adaptive immunity.

  18. Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

    Energy Technology Data Exchange (ETDEWEB)

    Fukuyama, Yoshiko; Tokuhara, Daisuke [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Sekine, Shinichi [Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University, Osaka 565-0871 (Japan); Kataoka, Kosuke [Department of Preventive Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Markham, Jonathan D.; Irwin, Allyson R.; Moon, Grace H.; Tokuhara, Yuka; Fujihashi, Keiko [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Davydova, Julia; Yamamoto, Masato [Department of Surgery, University of Minnesota, Minneapolis, MN 55455 (United States); Gilbert, Rebekah S. [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Fujihashi, Kohtaro, E-mail: kohtarof@uab.edu [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Nasal Ad-FL effectively up-regulates APC function by CD11c{sup +} DCs in mucosal tissues. Black-Right-Pointing-Pointer Nasal Ad-FL induces Notch ligand (L)-expressing CD11c{sup +} DCs. Black-Right-Pointing-Pointer Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c{sup +} dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c{sup +} DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FL activated CD11c{sup +} DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c{sup +} DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4{sup +} T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-{gamma}, IL-2 and IL-4 producing CD4{sup +} T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch-Notch-L pathway. These results show that Ad-FL induces CD11c{sup +} DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.

  19. Immunological interactions between 2 common pathogens, Th1-inducing protozoan Toxoplasma gondii and the Th2-inducing helminth Fasciola hepatica.

    Directory of Open Access Journals (Sweden)

    Catherine M D Miller

    Full Text Available BACKGROUND: The nature of the immune response to infection is dependent on the type of infecting organism. Intracellular organisms such as Toxoplasma gondii stimulate a Th1-driven response associated with production of IL-12, IFN-gamma, nitric oxide and IgG2a antibodies and classical activation of macrophages. In contrast, extracellular helminths such as Fasciola hepatica induce Th2 responses characterised by the production of IL-4, IL-5, IL-10 and IgG1 antibodies and alternative activation of macrophages. As co-infections with these types of parasites commonly exist in the field it is relevant to examine how the various facets of the immune responses induced by each may influence or counter-regulate that of the other. PRINCIPAL FINDINGS: Regardless, of whether F. hepatica infection preceded or succeeded T. gondii infection, there was little impact on the production of the Th1 cytokines IL-12, IFN-gamma or on the development of classically-activated macrophages induced by T. gondii. By contrast, the production of helminth-specific Th2 cytokines, such as IL-4 and IL-5, was suppressed by infection with T. gondii. Additionally, the recruitment and alternative activation of macrophages by F. hepatica was blocked or reversed by subsequent infection with T. gondii. The clinical symptoms of toxoplasmosis and the survival rate of infected mice were not significantly altered by the helminth. CONCLUSIONS: Despite previous studies showing that F. hepatica suppressed the classical activation of macrophages and the Th1-driven responses of mice to bystander microbial infection, as well as reduced their ability to reject these, here we found that the potent immune responses to T. gondii were capable of suppressing the responses to helminth infection. Clearly, the outcome of particular infections in polyparasitoses depends on the means and potency by which each pathogen controls the immune response.

  20. Characterization of T-lymphocytes in the anterior uvea of eyes with chronic equine recurrent uveitis.

    Science.gov (United States)

    Gilger, B C; Malok, E; Cutter, K V; Stewart, T; Horohov, D W; Allen, J B

    1999-10-01

    Equine recurrent uveitis (ERU), a chronic, recurrent inflammation primarily of the anterior uveal tract, is the most common cause of blindness in horses. Recently, T-lymphocytes have been found to be the most numerous cell type to infiltrate the anterior uveal of horses with ERU. In the present study, we characterized the T-lymphocyte population in the anterior uveal tract of eyes of horses with chronic ERU by evaluating the microscopic appearance (histopathologic features), the T-lymphocyte subsets, and the relative levels and amounts of T-lymphocyte cytokine mRNA in the anterior uvea. Seven inflamed eyes (from six horses with chronic ERU) and 5 normal eyes (from five horses with nonocular problems) were studied. After clinical examination, the eyes were removed, ocular fluids were aspirated, and anterior uveal tissues (iris and ciliary body) were processed for histologic and molecular (RNA isolation) analyses. Histologic examination by hematoxylin and eosin (H and E) staining and immunohistochemistry evaluating T-lymphocyte subsets (anti-CD4, CD8, CD5) were performed for each sample. RNA samples were analyzed for levels of messenger (m) RNA specific for interleukin (IL)-2, 4, and interferon-gamma (IFNgamma) by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). Eyes with ERU exhibited characteristic clinical signs, including corneal edema, aqueous flare, posterior synechia, corpora nigra degeneration, and cataract formation. Histologically, infiltration of the uveal tract with lymphocytes, plasma cells, and macrophages was most evident in the ciliary body and base of the iris. Loss of tissue structure (destruction) was most evident in the ciliary processes. Infiltrating lymphocytes were predominantly CD4+ T-cells (e.g. 48% CD4+ and 18% CD8+ in the ciliary body stroma), as determined by immunohistochemistry. Few inflammatory cells were observed in the normal eyes. The QRT-PCR results revealed increased transcription of IL-2 and IFNgamma and low

  1. Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

    NARCIS (Netherlands)

    De Simone, M.; Arrigoni, A.; Rossetti, G.; Gruarin, P.; Ranzani, V.; Politano, C.; Bonnal, R.J.; Provasi, E.; Sarnicola, M.L.; Panzeri, I.; Moro, M.; Crosti, M.; Mazzara, S.; Vaira, V.; Bosari, S.; Palleschi, A.; Santambrogio, L.; Bovo, G.; Zucchini, N.; Totis, M.; Gianotti, L.; Cesana, G.; Perego, R.A.; Maroni, N.; Pisani Ceretti, A.; Opocher, E.; De Francesco, R.; Geginat, J.; Stunnenberg, H.; Abrignani, S.; Pagani, M.

    2016-01-01

    Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or

  2. Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

    NARCIS (Netherlands)

    De Simone, M.; Arrigoni, A.; Rossetti, G.; Gruarin, P.; Ranzani, V.; Politano, C.; Bonnal, R.J.; Provasi, E.; Sarnicola, M.L.; Panzeri, I.; Moro, M.; Crosti, M.; Mazzara, S.; Vaira, V.; Bosari, S.; Palleschi, A.; Santambrogio, L.; Bovo, G.; Zucchini, N.; Totis, M.; Gianotti, L.; Cesana, G.; Perego, R.A.; Maroni, N.; Pisani Ceretti, A.; Opocher, E.; De Francesco, R.; Geginat, J.; Stunnenberg, H.; Abrignani, S.; Pagani, M.

    2016-01-01

    Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or

  3. Effects of antigen presentation of eosinophils on lung Th1/Th2 imbalance

    Institute of Scientific and Technical Information of China (English)

    XIE Zheng-fu; SHI Huan-zhong; QIN Xue-jun; KANG Lan-fu; HUANG Chun-ping; CHEN Yi-qiang

    2005-01-01

    Background Antigen-loaded eosinophils (EOSs) instilled intratracheally into mice were capable of inducing Th2-type cytokine production in the draining lymph nodes. The aim of the present study was to evaluate whether EOSs within the tracheobronchial lumen can stimulate Th2 cell expansion in the lung tissues.Methods Airway EOSs were recovered from ovalbumin-sensitized and -challenged BALB/c mice, these EOSs were then cocultured with CD4+ cells isolated from sensitized mice in the absence or presence of anti-CD80 or/and -CD86 monoclonal antibodies. Airway EOSs were instilled into the trachea of sensitized mice. At the day 3 thereafter, the lung tissues were removed and prepared into cell suspensions for culture. Cell-free culture supernatants were collected for detection of cytokines.Results Airway EOSs functioned as CD80- and CD86-dependent antigen-presenting cells to stimulate lung CD4+ lymphocytes to produce interleukin-4, interleukin-5 and interleukin-13, but not interferon-γ in in vitro assay. When instilled intratracheally in sensitized recipient mice, airway EOSs primed lung Th2 cells in vivo for interleukin-4, interleukin-5 and interleukin-13, but not interferon-γ, production during the in vitro culture that was also CD80- and CD86-dependent. Conclusion EOSs within the lumina of airways could process inhaled antigen and function in vitro and in vivo as antigen-presenting cells to promote expansion of Th2 cells in the lungs.

  4. The change of toll-like receptor 4 on peripheral blood mononuclear cells and the serum Thl/Th2 cytokine levels in patients with chronic hepatitis B receiving interferon-α therapy%α-干扰素治疗慢性乙型肝炎患者外周血单个核细胞TLR4表达和血清Th1/Th2型细胞因子的变化

    Institute of Scientific and Technical Information of China (English)

    李文莉; 吴茂盛; 黄育波; 刘细玲; 朱计芬; 许瑞荣

    2012-01-01

    Objective To investigate the change of toll-like receptor 4 on peripheral blood mononuclear cells and the serum Thl/Th2 cytokine levels in patients with chronic hepatitis B receiving interferon-a therapy. Methods 50 patients with chronic hepatitis B were treated with interferon a for six months. After 12 weeks, they were devided into response and non-response group. Serum HBV DNA was detected by PCR;The Thl/Th2 cytokines were measured by ELISA;TLR4 was measured by flow cytometry. Results The IL-4 and TLR4 c ontents in the two groups at 3rd and 6th month were significantly lower than that before interferon-α therapy (P0.05). Conclusions The changes of IFN-γ and IL-4 level in CHB patients received 12 week interferon-α therapy may be not releted to the changes of TLR4 level; the changes of TLR4 level probably is releted to the early response in CHB patients received interferon-a therapy.%目的 探讨慢性乙型肝炎患者在α-干扰素治疗前后外周血单个核细胞Toll样受体4(TLR4)的表达及血清Thl/Th2型细胞因子水平的变化及其临床意义.方法 50例HBeAg阳性慢性乙型肝炎患者予以普通α-干扰素治疗.在治疗前及治疗后3月和6月,使用流式细胞仪检测外周血单个核细胞表面TLR4表达;采用ELISA法检测血清IFN-γ和IL-4水平,并同时检测ALT、HBV DNA水平.结果 在治疗3个月和6个月时,早期应答组和无应答组患者血清IFN-γ水平均升高,IL-4水平均降低;两组TLR4水平较治疗前均下降,但应答组患者TLR4下降更明显,有显著性差异(P0.05),TLR4与ALT呈正相关(r=0.78,P<0.01),TLR4的变化与HBV DNA变化无相关(P>0.05).结论 在干扰素-α治疗后,慢性乙型肝炎患者Thl/Th2型细胞因子的变化可能与TLR4表达的变化无相关,而对干扰素治疗的疗效可能与TLR4表达的变化有关.

  5. Preventative effect of an herbal preparation (HemoHIM) on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

    Science.gov (United States)

    Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

    2013-01-01

    HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+) T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4(+) T cells displayed increased Th1 (IFN-γ(+) cell) as well as decreased Th2 (IL-4(+) cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.

  6. Preventative effect of an herbal preparation (HemoHIM on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

    Directory of Open Access Journals (Sweden)

    Jong-Jin Kim

    Full Text Available HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+ T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA. In an in vitro experiment, naive CD4(+ T cells displayed increased Th1 (IFN-γ(+ cell as well as decreased Th2 (IL-4(+ cell differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13 levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight pretreatment (4 weeks. These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.

  7. File list: DNS.Bld.05.AllAg.Th1_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.05.AllAg.Th1_Cells hg19 DNase-seq Blood Th1 Cells SRX069185,SRX201259,SRX20...1263,SRX201270,SRX193612,SRX037118,SRX201262 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.05.AllAg.Th1_Cells.bed ...

  8. File list: ALL.Bld.05.AllAg.Th1_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Th1_Cells hg19 All antigens Blood Th1 Cells SRX290723,SRX290666,SR...8,SRX290649 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.05.AllAg.Th1_Cells.bed ...

  9. Th9 cytokines response and its possible implications in the immunopathogenesis of leprosy.

    Science.gov (United States)

    de Sousa, Jorge Rodrigues; Pagliari, Carla; de Almeida, Dandara Simone Maia; Barros, Luiz Fernando Lima; Carneiro, Francisca Regina Oliveira; Dias, Leonidas Braga; de Souza Aarão, Tinara Leila; Quaresma, Juarez Antonio Simões

    2017-06-01

    Leprosy is an infectious-contagious disease whose clinical evolution depends on the interaction of the infectious agent with the immune response of the host, leading to a clinical spectrum that ranges from lepromatous leprosy (susceptibility, LL) to tuberculoid leprosy (resistance, TT). The immune response profile will depend on the pattern of cytokine production and on the activity of macrophages during infection. Classically, the clinical evolution of leprosy has been associated with Th1/Th2 cytokine profiles, but the role of new cytokine profiles such as T helper 9 (Th9) remains to be elucidated. To evaluate the tissue expression profile of these cytokines, a cross-sectional study was conducted using a sample of 30 leprosy skin lesion biopsies obtained from patients with leprosy, 16 TT and 14 lepromatous LL. Immunohistochemical analysis revealed a significant difference in interleukin (IL)-9, IL-4 transforming growth factor (TGF)-β and IL-10 levels between the two groups. IL-9 was more expressed in TT lesions compared with LL lesions. Higher expression of IL-4, IL-10 and TGF-β was observed in LL compared with TT. IL-4, IL-10 and TGF-β tended to be negatively correlated with the expression of IL-9, indicating a possible antagonistic activity in tissue. The results suggest that Th9 lymphocytes may be involved in the response to Mycobacterium leprae, positively or negatively regulating microbicidal activity of the local immune system in the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Cytokines and HCV-Related Disorders

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2012-01-01

    However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN-gamma-inducible CXC chemokine ligand (CXCL-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process.

  11. Study on the blood-borne virus co-infection and T lymphocyte subset among intravenous drug users

    Institute of Scientific and Technical Information of China (English)

    Jian-Rong Li; Rui-Yu Gong; Kun-Lun Tian; Jing Wang; Yi-Xin Wang; Han-Ju Huang

    2007-01-01

    AIM: To investigate the features of various bloodborne virus infections and co-infection in intravenous drug users (IDUs), and to examine the correlation of T lymphocyte subsets with virus co-infection.METHODS: Four hundred and six IDUs without any clinical manifestation of hepatitis and 102 healthy persons were enrolled in this study. HBV-DNA and HCV-RNA were detected by fluorescence quantitative PCR. HBsAg, HBeAg, anti-HBc, anti-HCV, HDV-Ag, anti-HGV, anti-HIV, and HCMV-IgM were assayed by enzyme-linked immunosorbent assay (ELISA) and immunochromatographic tests. The levels of Th1 and Th2 cytokines were measured by ELISA and radioactive immune assay (RIA). The T lymphocyte subpopulation was detected by using fluorescence immunoassay. The similar indices taken from the healthy persons served as controls.RESULTS: The viral infection rate among IDUs was 36.45% for HBV, 69.7% for HCV, 47.3% for HIV, 2.22% for HDV, 1.97% for HGV, and 3.45% for HCMV. The co-infection rate of blood-borne virus was detected in 255 of 406 (62.81%) IDUs. More than 80% (161/192) of subjects infected with HIV were co-infected with the other viruses, such as HBV, HCV. In contrast, among the controls, the infection rate was 17.65% for HBV and 0% for the other viruses. Our investigation showed that there was a profound decrease in the proportion of CD4/CD8 and the percentage of CD3 and CD4, but not in the percentage of CD8. The levels of PHA-induced cytokines (IFN-γ and IL-4) and serum IL-2 were obviously decreased in IDUs. On the other hand, the level of serum IL-4 was increased. The level of IFN-γ and the percentage of CD4 were continuously decreased when the IDUs were infected with HIV or HIV co-infection. IDUs with HIV and HBV co-infection was 15.1% (29/192). Of those 29 IDU with HIV and HBV co-infection, 51.72% (15/29) and 37.93% (11/29) were HBV-DNA-positive and HBeAg-positive, respectively. But, among IDUs without HIV infection, only 1.68% (2/119) of cases were HBV

  12. Envelope specific T cell responses & cytokine profiles in chikungunya patients hospitalized with different clinical presentations

    Science.gov (United States)

    Tripathy, Anuradha S.; Tandale, Babasaheb V.; Balaji, Saravana S.; Hundekar, Supriya L.; Ramdasi, Ashwini Y.; Arankalle, Vidya A.

    2015-01-01

    Background & objectives: Since the 2006 massive outbreaks, chikungunya (CHIK) is a major public health concern in India. The aim of this study was to assess envelope specific immune responses in patients with chikungunya infection. Methods: This study included 46 hospitalized patients with chikungunya virus infection (encephalitis, n=22, other systemic involvement, OSI, n=12, classical, n=12) and six controls from Ahmedabad city, Gujarat, India. T cell responses and the levels of Th1, pro/ anti-inflammatory cytokines against the CHIK virus envelope antigens were assessed by lymphocyte proliferation assay and by cytometric bead array in flow cytometry, respectively. Results: Lymphoproliferative response was uniform among the patients. Comparisons of cytokines revealed significantly higher levels of interleukin (IL)-4 and IL-5 in encephalitis, OSI and classical patients versus controls. The levels of tumour necrosis factor (TNF)-α were higher in classical patients categories compared to the controls. Interferon (IFN)-γ levels were lower in encephalitis patients versus control. Interpretation & conclusions: Our findings showed recognition of T cell epitopes on the envelope region of chikungunya virus by all patient categories. Lower level of IFN-γ may be associated with the severity of disease in these patients. PMID:25900956

  13. Ganoderma lucidum polysaccharides encapsulated in liposome as an adjuvant to promote Th1-bias immune response.

    Science.gov (United States)

    Liu, Zhenguang; Xing, Jie; Zheng, Sisi; Bo, Ruonan; Luo, Li; Huang, Yee; Niu, Yale; Li, Zhihua; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo; Wu, Yi

    2016-05-20

    Liposome-based vaccine delivery systems are known to enhance immune responses. Ganoderma lucidum polysaccharides (GLP) have been widely studied as immunomodulator and it could be as inducers of strong immune responses. In the research, GLP and ovalbumin (OVA) were encapsulated into liposome as vaccine and inoculated to mice. The magnitude and kinetics of the humoral and cellular immune responses were investigated. The results showed that GLP-OVA-loaded liposomes (GLPL/OVA) could induce more powerful antigen-specific immune responses than each single-component formulation. Mice immunized with GLPL/OVA displayed higher antigen-specific IgG antibodies, better splenocytes proliferation, higher cytokine secretion by splenocytes and significant activation of CD3+CD4+ and CD3+CD8+ T cells. Thus the GLPL/OVA formulation produced a heightened humoral and cellular immune response, with an overall Th1 bias. Enhanced immune responses elicited by the GLPL/OVA formulation might be attributed to effective activation and mature of DC in draining lymph nodes. Overall, these findings indicate that GLPL have the potential to enhance immune responses as vaccine delivery systems.

  14. The effect of size-segregated ambient particulate matter on Th1/Th2-like immune responses in mice

    Science.gov (United States)

    Liu, Szu-Yuan; Chou, Charles C. K.; Lee, Yi-Hsin; Cheng, Tsun-Jen

    2017-01-01

    Background Particulate matter (PM) has been associated with increased pulmonary and cardiovascular mortality and morbidity. Additionally, PM is known to exacerbate asthma. However, whether ambient PM exposure contributes to the onset of asthma, especially in non-atopic children and adults, is less conclusive. The current study aimed to evaluate the effects of size-fractioned PM on lung immune responses in healthy BALB/c mice. Methods and principal findings We collected PM10, PM2.5, PM1 and PM0.1 samples from October 2012 to August 2013 in the Taipei Basin. These PM samples were representative of urban traffic pollution. The samples were extracted and sonicated in phosphate-buffered saline (PBS). Female BALB/c mice were exposed to the samples via intratracheal instillation at three different doses: 1.75 mg/kg (35 μg/per mouse), 5 mg/kg (100 μg/per mouse), and 12.5 mg/kg (250 μg/per mouse). The mice were exposed on days 0 and 7, and PBS alone was used as a control. Following the exposures, the expression profiles of inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were assessed. Exposure to PM10 resulted in inflammatory responses, including the recruitment of neutrophils and the induction of T helper 1 (Th1) cell-related cytokine release, such as TNF-α and IFN-γ. Furthermore, an allergic immune response, including the recruitment of eosinophils and the up-regulation of T helper 2 (Th2) cell-related cytokine release, such as IL-5 and IL-13, was also observed in the BALF of mice exposed to PM10. Conclusions Our study showed that exposure to PM alone caused mixed Th1/Th2 inflammatory responses in healthy mice. These findings support the hypothesis that PM may contribute to the onset of asthma. PMID:28245275

  15. Comparison of Th1 and Th2 responses in non-healing and healing patients with cutaneous leishmaniasis

    Science.gov (United States)

    Shahi, Maryam; Mohajery, Masoud; Shamsian, Seyyed Ali Akbar; Nahrevanian, Hossein; Yazdanpanah, Seyyed Mohammad Javad

    2013-01-01

    Background: Cutaneous leishmaniasis is an endemic disease in many regions of Iran, including the city of Mashhad. In recent years, some cases have not responded to Glucantime, the usual treatment for this disease. The cellular immune response caused by T-helper type 1 (Th1) cells has an important role in protection against leishmaniasis, and activation of the T-helper type 2 (Th2) response causes progression of the disease. By analyzing these responses we hope to find a more effective treatment than that currently in use for leishmaniasis patients. Methods: The cellular immune responses in 60 cases of non-healing and healing cutaneous leishmaniasis, and individuals in a control group, were analyzed by measuring cytokines released by peripheral blood mononuclear cells (PBMCs) when stimulated with Leishmania major antigens by Enzyme Linked Immuno Sorbent Assay (ELISA). Results: Subjects from the healing group secreted more interleukin-12 (IL-12) and interferon gamma (IFN-γ) (p<0.05) and less interleukins -4, -5, -10 (IL-4, IL-5, and IL-10) (p<0.005) and -18 (IL-18) (p=0.003) than the non-healing group. Conclusions: The results demonstrate that secretion of cytokines that activate Th2 response including IL-4, IL-5 and IL-10 in non-healing subjects was higher than healing subjects and secretion of cytokines that activate Th1 response including IL-12 and IFN-γ in healing subjects was higher relative to the non-healing subjects. In this study it has been shown that the level of IL-18 progresses disease in non-healing patients when the level of IL-12 gets decreased. PMID:26989708

  16. T-Helper Cytokine Profiles in Patients with Kawasaki Disease.

    Science.gov (United States)

    Lee, Sang Bum; Kim, Young Hyun; Hyun, Myung Chul; Kim, Yeo Hyang; Kim, Hee Sun; Lee, Young Hwan

    2015-11-01

    Kawasaki disease is an acute systemic vasculitis of which pathogenesis suspected is caused by immune dysregulation. The goal of this study is to evaluate the activation pattern of T helper cell type 1 (Th1) and T helper cell type 2 (Th2) in patients with Kawasaki disease. Prospective study of 60 patients (male 36, female 24) with diagnosis of Kawasaki disease were enrolled. One hundred and eighty blood samples from these patients were collected according to the different clinical stages {before initial intravenous immunoglobulin (IVIG), 5 days after initial IVIG, 2 months after initial IVIG}. The plasma level of Th1 cytokines; interferon-gamma (IFN-γ) & interleukin (IL)-2 and Th2 cytokines; IL-4 & IL-10 were measured by enzyme-liked immunosorbent assay. In all patients, the plasma level of Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4 and IL-10) were markedly elevated during the acute stage of Kawasaki disease. Since then, the plasma level of all these cytokines decreased significantly along with the process of clinical stages. Regardless of the existence of coronary artery lesion or no response to initial IVIG treatment, there were no significant differences between them. These data suggest that both Th1 and Th2 cells may be activated simultaneously during the acute stage of Kawasaki disease. Further studies are therefore required to establish the difference of activation pattern of T helper cells between Kawasaki disease and other inflammatory diseases.

  17. THE ROLE OF THE DIFFERENT SUBPOPULATIONS OF CD4+Т LYMPHOCYTES DURING PREGNANCY

    Directory of Open Access Journals (Sweden)

    D. I. Sokolov

    2016-01-01

    Full Text Available An important role in the formation of immunological tolerance during pregnancy play T lymphocytes. In the present review discusses the characteristics of T lymphocytes, decidua and placenta, especially their migration and functional activity during pregnancy. The review discusses the role of the subpopulations of Th1, Th17, Th2 and Treg lymphocytes in the formation of the placenta and the immune regulation of pregnancy, as well as their interaction with the cells of the decidua and trophoblast.

  18. Cytokines in lethal graft-versus-host disease

    NARCIS (Netherlands)

    Knulst, A.C.; Bril-Bazuin, C.; Tibbe, G.J.M.; Oudenaren, van A.; Savelkoul, H.F.J.; Benner, R.

    1992-01-01

    Graft-versus-host disease (GVHD) is caused by donor T lymphocytes that recognize foreign antigens on host tissues. This leads to T cell activation, which involves a cascade of events including the transcription of genes for cytokines and their receptors and the production of cytokines. One of the fi

  19. Th1/Th2细胞在心肌梗死中的作用%The Role of Thl/Th2 Cells in the Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    曹磊; 迟锦玉; 刘文秀; 刘越; 尹新华

    2013-01-01

    Th1/Th2 cytokine balance is an important factor for normal immune status to maintain body balance.Its disorder is associated with many diseases,such as infectious diseases,autoimmune diseases,cancer,and cardiovascular disease.The inflammatory reaction has always been in the occurrence and development of myocardial infarction.Lesions of the myocardial cells and other inflammatory cells could produce large amounts of inflammatory cytokines and mediators of inflammation.Research has shown that these cytokines influence on myocardial remodeling.The inflammatory reaction has always been in the occurrence and development of myocardial infarction.Lesions of the myocardial cells and other inflammatory cells could produce large amounts of inflammatory cytokines and mediators of inflammation.Research has shown that these cytokines influence on myocardial remodeling.In recent years,the balance of Th1/Th2 and cardiovascular disease have become the focus of study.Acute myocardial infarction related to the onset of the immune response is attracting more and more attention.This paper makes a brief review on the role of Thl/Th2 cells in myocardial infarction.%Th1/Th2细胞因子平衡对于维持机体的正常免疫状态是重要因素,其平衡的紊乱与很多疾病密切相关,如感染性疾病、自身免疫性疾病、肿瘤、心血管疾病等.在心肌梗死的发生发展过程中存在炎症反应,病变的心肌细胞及其他炎症细胞均可产生大量炎症细胞因子和炎症介质,有研究证实这些细胞因子影响心肌重构.近年来关于Th1/Th2细胞因子的平衡与心血管疾病的关系已成为研究的重点.急性心肌梗死的发作与免疫应答的关系越来越引起人们的关注.本文就Th1/rh2细胞在心肌梗死中的作用做一简要综述.

  20. Use of flow cytometry to investigate the cytokine response pattern in infants with respiratory syncytial virus infection and bronchiolitis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:To investigate the cytokine response pattern(IL-4/IFN-γ)in infants with RSV infections and bronchiolitis during the acute phase,Methods:Four-color flow cytometry was used to measure intracellular IL-4 and IFN-γ expressions in peripheral blood CD3+ and CD*+ lymphocytes from RSV-infected and bronchiolitis infants.Serum IL-4 and INF-γ levels were also determined.Results:RSV-infected and bronchiolitis infants showed no statistical differences from not-RSV-infected or pneumonia infants and control in the frequency of IL-4 and INF-γ levels were also determined.Results;RSV-infected and bronchiolitis infants showed no statistical differences from not-RSV-infected or pneumonia infants and control in the frequency of IL-4 and IFN-γ expressions in CD3+CD8- lymphocytes,showed no obvious Th1/Th2 imbalance,while IFN-γ was expressed much more frequently in CD3+CD*+ lymphocytes.Systematically,RSV-infected and bronchiolitis infants showed moch lower levels of serum IL-4 and IL-4/INF-γ ratios and much higher serum IFN-γ levels than control.Howerver,there were no statistical differences in the above three indices between RSV-infected and not-RSV infected infants or between bronchiolitis and pneumonia infants,except that bronchiolitis infants had a higher level of serum INF-γ than pneumonia infants statistically .Conclusions:There is no type-2 cytokine response predominance in the acute thase of RSV infection and bronchilitis.IL-4 productioin is suppressed and IFN-γ production upregulated,the latter being most prominent in bronchiolitis infants.

  1. γδ T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-α and IFN-γ-producers in response to Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Martínez Natalia

    2003-09-01

    Full Text Available Abstract Background γδ T cells have an important immunoregulatory and effector function through cytokine release. They are involved in the responses to Gram-negative bacterium and in protection of lung epithelium integrity. On the other hand, they have been implicated in airway inflammation. Methods The aim of the present work was to study intracytoplasmic IL-2, IL-4, IFN-γ and TNF-α production by γδ and αβ T lymphocytes from cystic fibrosis patients and healthy donors in response to Pseudomonas aeruginosa (PA. Flow cytometric detection was performed after peripheral blood mononuclear cells (PBMC culture with a cytosolic extract from PA and restimulation with phorbol ester plus ionomycine. Proliferative responses, activation markers and receptor usage of γδ T cells were also evaluated. Results The highest production of cytokine was of TNF-α and IFN-γ, γδ being better producers than αβ. No differences were found between patients and controls. The Vγ9δ2 subset of γδ T cells was preferentially expanded. CD25 and CD45RO expression by the αβ T subset and PBMC proliferative response to PA were defective in cystic fibrosis lymphocytes. Conclusion Our results support the hypothesis that γδ T lymphocytes play an important role in the immune response to PA and in the chronic inflammatory lung reaction in cystic fibrosis patients. They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

  2. Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord.

    Science.gov (United States)

    Hu, Jian-Guo; Shi, Ling-Ling; Chen, Yue-Juan; Xie, Xiu-Mei; Zhang, Nan; Zhu, An-You; Jiang, Zheng-Song; Feng, Yi-Fan; Zhang, Chen; Xi, Jin; Lü, He-Zuo

    2016-03-01

    Myelin basic protein (MBP) activated T cells (MBP-T) play an important role in the damage and repair process of the central nervous system (CNS). However, whether these cells play a beneficial or detrimental role is still a matter of debate. Although some studies showed that MBP-T cells are mainly helper T (Th) cells, their subtypes are still not very clear. One possible explanation for MBP-T immunization leading to conflicting results may be the different subtypes of T cells are responsible for distinct effects. In this study, the Th1 and Th2 type MBP-T cells (MBP-Th1 and -Th2) were polarized in vitro, and their effects on the local immune microenvironment and tissue repair of spinal cord injury (SCI) after adoptive immunization were investigated. In MBP-Th1 cell transferred rats, the high levels of pro-inflammatory cells (Th1 cells and M1 macrophages) and cytokines (IFN-γ, TNF-α, -β, IL-1β) were detected in the injured spinal cord; however, the anti-inflammatory cells (Th2 cells, regulatory T cells, and M2 macrophages) and cytokines (IL-4, -10, and -13) were found in MBP-Th2 cell transferred animals. MBP-Th2 cell transfer resulted in decreased lesion volume, increased myelination of axons, and preservation of neurons. This was accompanied by significant locomotor improvement. These results indicate that MBP-Th2 adoptive transfer has beneficial effects on the injured spinal cord, in which the increased number of Th2 cells may alter the local microenvironment from one primarily populated by Th1 and M1 cells to another dominated by Th2, Treg, and M2 cells and is conducive for SCI repair.

  3. Altered Immune Cytokine Expression Associated with KoRV B Infection and Season in Captive Koalas.

    Science.gov (United States)

    Maher, Iona E; Higgins, Damien P

    2016-01-01

    Koala (Phascolarctos cinereus) populations are increasingly vulnerable and one of the main threats is chlamydial infection. Koala retrovirus (KoRV) has been proposed as an underlying cause of the koala's susceptibility to infection with Chlamydia and high rates of lymphoid neoplasia; however, the regionally ubiquitous, endogenous nature of this virus suggests that KoRV A infection is not sufficient for immune suppression to occur. A recently discovered exogenous variant of KoRV, KoRV B, has several structural elements that cause increased pathogenicity in related retroviruses and was associated with lymphoid neoplasia in one study. The present study assesses whether KoRV B infection is associated with alterations in immune function. Cytokine gene expression by mitogen stimulated lymphocytes of KoRV B positive (n = 5-6) and negative (n = 6-7) captive koalas was evaluated by qPCR four times (April 2014-February 2015) to control for seasonal variation. Key immune genes in the Th1 pathway (IFNγ, TNFα), Th2 pathway (IL 10, IL4, IL6) and Th17 pathway (IL17A), along with CD4:CD8 ratio, were assessed. KoRV B positive koalas showed significantly increased up-regulation of IL17A and IL10 in three out of four sampling periods and IFNγ, IL6, IL4 and TNFα in two out of four. IL17A is an immune marker for chlamydial pathogenesis in the koala; increased expression of IL17A in KoRV B positive koalas, and concurrent immune dysregulation, may explain the differences in susceptibility to chlamydial infection and severity of disease seen between individuals and populations. There was also marked seasonal variation in up-regulation for most of the cytokines and the CD4:CD8 ratio. The up-regulation in both Th1 and Th2 cytokines mirrors changes associated with immune dysregulation in humans and felids as a result of retroviral infections. This is the first report of altered immune expression in koalas infected by an exogenous variant of KoRV and also the first report of seasonal

  4. Human leukocyte antigen-G expression in differentiated human airway epithelial cells: lack of modulation by Th2-associated cytokines

    Directory of Open Access Journals (Sweden)

    White Steven R

    2013-01-01

    Full Text Available Abstract Background Human leukocyte antigen (HLA-G is a nonclassical class I antigen with immunomodulatory roles including up-regulation of suppressor T regulatory lymphocytes. HLA-G was recently identified as an asthma susceptibility gene, and expression of a soluble isoform, HLA-G5, has been demonstrated in human airway epithelium. Increased presence of HLA-G5 has been demonstrated in bronchoalveolar lavage fluid recovered from patients with mild asthma; this suggests a role for this isoform in modulating airway inflammation though the mechanisms by which this occurs is unclear. Airway inflammation associated with Th2 cytokines such as IL-4 and IL-13 is a principal feature of asthma, but whether these cytokines elicit expression of HLA-G is not known. Methods We examined gene and protein expression of both soluble (G5 and membrane-bound (G1 HLA-G isoforms in primary differentiated human airway epithelial cells collected from normal lungs and grown in air-liquid interface culture. Cells were treated with up to 10 ng/ml of either IL-4, IL-5, or IL-13, or 100 ng/ml of the immunomodulatory cytokine IL-10, or 10,000 U/ml of the Th1-associated cytokine interferon-beta, for 24 hr, after which RNA was isolated for evaluation by quantitative PCR and protein was collected for Western blot analysis. Results HLA-G5 but not G1 was present in dAEC as demonstrated by quantitative PCR, western blot and confocal microscopy. Neither G5 nor G1 expression was increased by the Th2-associated cytokines IL-4, IL-5 or IL-13 over 24 hr, nor after treatment with IL-10, but was increased 4.5 ± 1.4 fold after treatment with 10,000 U/ml interferon-beta. Conclusions These data demonstrate the constitutive expression of a T lymphocyte regulatory molecule in differentiated human airway epithelial cells that is not modulated by Th2-associated cytokines.

  5. [Cytokines in bone diseases. What is cytokine?].

    Science.gov (United States)

    Murakami, Yousuke; Kohsaka, Hitoshi

    2010-10-01

    Cytokines have an essential role for cell-cell communication. They can regulate cell proliferation, differentiation, survival, and function. Interaction of cell surface receptor with cytokines is necessary for control of physiological responses. Activation of cytokine receptors transduces specific signal in the receptor-expressing cells, resulting that cytokines can regulate specific cell population. Thus, cytokines contribute directly or indirectly to morphogenesis, host defense and immune response, play critical roles for homeostasis and development.

  6. Changes in Th1 cells and CD4+CD25+Treg cells in non-obese diabetic mice at early stage of diabetes

    Directory of Open Access Journals (Sweden)

    Hong-jun WANG

    2013-11-01

    Full Text Available Objective To investigate the changes in Th1 cells and CD4+CD25+Treg cells in non-obese diabetic (NOD mice at early stage of diabetes, and to evaluate the significance of these changes. Methods Four week- (group A, 8 week- (group B and 16 week-old (group C female NOD mice (8 each were used in present study. The spleen, thymus and pancreas were harvested. Th1 and CD4+CD25+Treg cells in spleen were determined by flow cytometer, and the ratios of Th1/CD4+T, CD4+CD25+Treg/CD4+T and Th1/CD4+CD25+Treg were calculated. Subsequently, CD4–CD8–T, CD4+CD8+T, CD4–CD8+T and CD4+CD8–T cells in thymus were determined by flow cytometer, and the ratio of CD25+Treg/CD4+CD8–T was calculated. The histopathological changes in pancreas were also evaluated by HE staining and immunohistochemistry staining. Results The proportion of Th1 cells in spleen and the ratios of Th1/CD4+T and Th1/CD4+CD25+Treg were higher significantly in group C than in group A and B. However, no significant differences were found in the proportion of spleen CD4+CD25+Treg cells and the ratio of CD4+CD25+Treg/CD4+T among the three groups. Compared with group A, no obvious changes were found in thymus CD4–CD8–T, CD4+CD8+T, CD4–CD8+T and CD4+CD8–T cells in group B and C, but the ratio of thymus CD25+Treg/CD4+CD8–T increased significantly in group B and C. Lymphocytic infiltration was observed in pancreatic islets of group B and C as shown with HE staining, but Foxp3+T cells were not seen in pancreatic islets by immunohistochemistry. Conclusion Th1 cells are gradually increased at early stage of diabetes in NOD mice, but CD4+CD25+Treg cells are relatively default. These changes may play an important role in the progress of diabetes. DOI: 10.11855/j.issn.0577-7402.2013.11.004

  7. Activation of dendritic cells by the Gal-lectin of Entamoeba histolytica drives Th1 responses in vitro and in vivo.

    Science.gov (United States)

    Ivory, Catherine P A; Chadee, Kris

    2007-02-01

    Amebiasis is a human disease caused by the protozoan intestinal parasite Entamoeba histolytica. Vaccine development has focused on the parasite's surface galactose-N-acetyl-D-galactosamine inhibitable lectin (Gal-lectin) as a protective antigen. The Gal-lectin is immunogenic and has been shown to induce Th1 cytokines in vitro and in vivo. The immunological basis of the protective immune response elicited by the Gal-lectin is unknown. In this study, we investigated the response of BALB/c bone marrow-derived DC to E. histolytica Gal-lectin. Incubation of immature DC with Gal-lectin resulted in activation and maturation after 24 h. FACS analysis demonstrated an up-regulation of DC maturation markers CD80, CD86, CD40 and MHC class II upon exposure to Gal-lectin. The Gal-lectin also induced DC production of IL-12, indicating a Th1 response. Gal-lectin-activated DC were able to stimulate T cell proliferation in an allogeneic mixed leukocyte reaction and adoptive transfer of Gal-lectin-treated DC into naïve mice resulted in IFN-gamma-producing Gal-lectin-sensitized T cells. The activation of DC by Gal-lectin was mediated by MAPK and NF-kappaB. These findings indicate that E. histolytica Gal-lectin is a potent vaccine antigen capable of directly initiating DC maturation and activation characterized by Th1 cytokine production.

  8. Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: estefaniabio@yahoo.com.br, e-mail: antero@cdtn.br; Resende, Maria Aparecida de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Microbiologia], e-mail: maresend@mono.icb.ufmg.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia], e-mail: goes@mono.icb.ufmg.br, e-mail: brsgarbi@mono.icb.ufmg.br

    2009-07-01

    Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - {gamma}, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-{gamma} production was maintained indicating that a Th1 pattern was

  9. Expression of nerve growth factor mRNA in splenic lymphocytes of bronchial asthma rats and its influencing actors

    Institute of Scientific and Technical Information of China (English)

    Jihong Dai; Yonghong Wang; Haixia He

    2008-01-01

    lymphocytes of the asthmatic model expressed NGF mRNA in a time-dependent manner. After lymphocytes were cultured with IL-13 at a final concentration of 50 μg/L for 12, 24 or 48 hours, expression of NGF mRNA was upregulated in a time-dependent manner to higher levels than the basal values at the same time points (P < 0.01). IL-13 upregulated the expression of NGF mRNA in a dose-dependent manner, and the NGF mRNA expression levels at middle and high concentrations of IL-3 were significantly higher than the values at a low concentration of IL-13 (P < 0.05). With increasing IFN-γconcentration, the expression of NGF mRNA was gradually downregulated. The low concentration group showed lower levels of NGF mRNA than the blank control group, while the middle and high concentration IFN-γgroups showed lower levels than the low concentration group (P < 0.05).CONCLUSION: In asthmatic rats, IL-13, a Th2 cytokine, upregulates the expression of NGF mRNA, while IFN-γ, a Th1 cytokine, downregulates NGF mRNA expression. The effects of both cytokines were time and dose dependent. Th1/Th2 cytokine immune imbalance may indirectly induce airway neurogenic inflammation by regulating NGF mRNA expression.

  10. Use of a Th1 Stimulator Adjuvant for Vaccination against Neospora caninum Infection in the Pregnant Mouse Model

    Directory of Open Access Journals (Sweden)

    Denis Grandgirard

    2013-03-01

    Full Text Available Vertical transmission from an infected cow to its fetus accounts for the vast majority of new Neospora caninum infections in cattle. A vaccine composed of a chimeric antigen named recNcMIC3-1-R, based on predicted immunogenic domains of the two microneme proteins NcMIC1 and NcMIC3, the rhoptry protein NcROP2, and emulsified in saponin adjuvants, significantly reduced the cerebral infection in non-pregnant BALB/c mice. Protection was associated with a mixed Th1/Th2-type cytokine response. However, the same vaccine formulation elicited a Th2-type immune response in pregnant mice and did not prevent vertical transmission or disease, neither in dams nor in offspring mice. In this study, an alternative vaccine formulation containing recNcMIC3-1-R emulsified in Freund’s incomplete adjuvant, a stimulator of the cellular immunity, was investigated. No protection against vertical transmission and cerebral infection in the pregnant mice and a very limited protective effect in the non-pregnant mice were observed. The vaccine induced a Th1-type immune response characterized by high IgG2a titres and strong IFN-γ expression, which appeared detrimental to pregnancy.

  11. Mycobacterium tuberculosis co-operonic PE32/PPE65 proteins alter host immune responses by hampering Th1 response

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    Mohd eKhubaib

    2016-05-01

    Full Text Available PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed and co-translated, and play role in modulating host immune responses. Experiments with macrophage cell lines revealed that this protein complex suppresses pro-inflammatory cytokines such as TNF-α and IL-6 whereas also inducing high expression of anti-inflammatory IL-10. Immunization of mice with these recombinant proteins dampens an effective Th1 response as evident from reduced frequency of IFN-g and IL-2 producing CD4+ and CD8+ T cells. IgG sub-typing from serum of immunized mice revealed high levels of IgG1 when compared with IgG2a and IgG2b. Further IgG1/IgG2a ratio clearly demonstrated that the protein complex manipulates the host immune response favourable to the pathogen. Our results demonstrate that the co-transcribed and co-translated PE32 and PPE65 antigens are involved specifically in modulating anti-mycobacterial host immune response by hampering Th1 response.

  12. Nocardia rubra cell-wall skeleton promotes CD4(+) T cell activation and drives Th1 immune response.

    Science.gov (United States)

    Wang, Guangchuan; Wu, Jie; Miao, Miao; Dou, Heng; Nan, Ning; Shi, Mingsheng; Yu, Guang; Shan, Fengping

    2017-03-15

    Several lines of evidences have shown that Nocardia rubra cell wall skeleton (Nr-CWS) has immunoregulatory and anti-tumor activities. However, there is no information about the effect of Nr-CWS on CD4(+) T cells. The aim of this study was to explore the effect of Nr-CWS on the phenotype and function of CD4(+) T cells. Our results of in vitro experiments showed that Nr-CWS could significantly up-regulate the expression of CD69 and CD25 on CD4(+) T cells, promote the proliferation of CD4(+) T cells, increase the production of IFN-γ, TNF-α and IL-2 in the supernatants, but has no significant effect on the apoptosis and death of CD4(+) T cells. Results of in vivo experiments showed that Nr-CWS could promote the proliferation of CD4(+) T cells, and increase the production of IL-2, IFN-γ and TNF-α (Th1 type cytokines). These data suggest that Nr-CWS can enhance the activation of CD4(+) T cells, promote the proliferation of CD4(+) T cells and the differentiation of CD4(+) T cells to Th1 cells.

  13. Coincident diabetes mellitus modulates Th1-, Th2-, and Th17-cell responses in latent tuberculosis in an IL-10- and TGF-β-dependent manner.

    Science.gov (United States)

    Kumar, Nathella Pavan; Moideen, Kadar; George, Parakkal Jovvian; Dolla, Chandrakumar; Kumaran, Paul; Babu, Subash

    2016-02-01

    Type 2 diabetes mellitus (DM) is a risk factor for the development of active tuberculosis (TB), although its role in the TB-induced responses in latent TB (LTB) is not well understood. Since Th1, Th2, and Th17 responses are important in immunity to LTB, we postulated that coincident DM could alter the function of these CD4(+) T-cell subsets. To this end, we examined mycobacteria-induced immune responses in the whole blood of individuals with LTB-DM and compared them with responses of individuals without DM (LTB-NDM). T-cell responses from LTB-DM are characterized by diminished frequencies of mono- and dual-functional CD4(+) Th1, Th2, and Th17 cells at baseline and following stimulation with mycobacterial antigens-purified protein derivative, early secreted antigen-6, and culture filtrate protein-10. This modulation was at least partially dependent on IL-10 and TGF-β, since neutralization of either cytokine resulted in significantly increased frequencies of Th1 and Th2 cells but not Th17 cells in LTB-DM but not LTB individuals. LTB-DM is therefore characterized by diminished frequencies of Th1, Th2, and Th17 cells, indicating that DM alters the immune response in latent TB leading to a suboptimal induction of protective CD4(+) T-cell responses, thereby providing a potential mechanism for increased susceptibility to active disease.

  14. Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum

    OpenAIRE

    Ostensen, M; Forger, F; Nelson, J.; Schuhmacher, A.; Hebisch, G; Villiger, P

    2004-01-01

    Objective: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS).

  15. Lymphocyte subsets in pediatric migraine.

    Science.gov (United States)

    Cseh, Aron; Farkas, Kristof Mark; Derzbach, Laszlo; Muller, Katalin; Vasarhelyi, Barna; Szalay, Balazs; Treszl, Andras; Farkas, Viktor

    2013-07-01

    Aseptic inflammation due to activated immune cells has been implicated in the pathomechanism of migraine. We measured the prevalence of regulatory T cells (Tregs), along with that of CD4(+)/CD8(+) lymphocytes and their Th1/Th2 commitment in pediatric migraine. Children and adolescents suffering from migraine without aura, migraine with aura and hemiplegic migraine ictally (n = 53, 27, and 20, respectively), also interictally (n = 33) were recruited and compared to 24 healthy children. Our results indicated comparable prevalence of Tregs, CD4(+) and Th1/Th2 committed cells. CD8(+) prevalence was lower, and CD4(+)/CD8(+) ratio was higher in ictal phase irrespective of the subtype of migraine. No association between CD8(+) prevalence and gender, body weight, disease onset and attack duration in migraine subtypes was found. CD8(+) prevalence was normal in patients in interictal phase. These results suggest the absence of major systemic alteration of adaptive immunity in children and adolescents suffering from migraine; however, a transient decrease of CD8(+) prevalence during the ictal phase was detected irrespective of the subtype of migraine.

  16. T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes

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    Zheng-Hong Di

    2016-01-01

    Conclusions: Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.

  17. A human vitamin D receptor mutation causes rickets and impaired Th1/Th17 responses.

    Science.gov (United States)

    van der Eerden, Bram C J; van der Heyden, Josine C; van Hamburg, Jan Piet; Schreuders-Koedam, Marijke; Asmawidjaja, Patrick S; de Muinck Keizer-Schrama, Sabine M; Boot, Annemieke M; Lubberts, Erik; Drop, Stenvert L S; van Leeuwen, Johannes P T M

    2014-12-01

    We present a brother and sister with severe rickets, alopecia and highly elevated serum levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D3). Genomic sequencing showed a homozygous point mutation (A133G) in the vitamin D receptor gene, leading to an amino acid change in the DNA binding domain (K45E), which was described previously. Hereditary vitamin D resistant rickets (HVDRR) was diagnosed. Functional studies in skin biopsy fibroblasts confirmed this. 1,25-(OH)2D3 reduced T helper (Th) cell population-specific cytokine expression of interferon γ (Th1), interleukins IL-17A (Th17) and IL-22 (Th17/Th22) in peripheral blood mononuclear cells (PBMCs) from the patient's parents, whereas IL-4 (Th2) levels were higher, reflecting an immunosuppressive condition. None of these factors were regulated by 1,25-(OH)2D3 in PBMCs from the boy. At present, both patients (boy is 23 years of age, girl is 7) have not experienced any major immune-related disorders. Although both children developed alopecia, the girl did so earlier than the boy. The boy showed complete recovery from the rickets at the age of 17 and does not require any vitamin D supplementations to date. In conclusion, we characterized two siblings with HVDRR, due to a mutation in the DNA binding domain of VDR. Despite a defective T cell response to vitamin D, no signs of any inflammatory-related abnormalities were seen, thus questioning an essential role of vitamin D in the immune system. Despite the fact that currently medicine is not required, close monitoring in the future of these patients is warranted for potential recurrence of vitamin D dependence and diagnosis of (chronic) inflammatory-related diseases.

  18. Th1、Th17细胞对小鼠视网膜星形细胞的杀伤作用%Interaction between mouse retinal astrocyte and antigen specific Th1 and Th17 Cells

    Institute of Scientific and Technical Information of China (English)

    崔彦; 毕宏生; Deming Sun

    2012-01-01

    light for mouse after immunization whereas it is prominent for B10R Ⅲ. Objective This study was to observe the killing effect of interphotoreceptor retinoid binding protein (IRBP) 1-20-specific T cells on mouse retinal astrocyte.Th1 and Th17 cells effect in the EAU mechanism was discussed.Methods B10RllⅢ mice and C57BL/6 mice were immunized with IRBP 161-180 and IRBP 1-20 in complete Freund adjuvant (CFA).The infiltrati