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Sample records for alpha chain cd25

  1. Prognostic Relevance of Cytokine Receptor Expression in Acute Myeloid Leukemia: Interleukin-2 Receptor α-Chain (CD25) Expression Predicts a Poor Prognosis

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    Nakase, Kazunori; Kita, Kenkichi; Kyo, Taiichi; Ueda, Takanori; Tanaka, Isao; Katayama, Naoyuki

    2015-01-01

    A variety of cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, little is known about the clinical relevance of cytokine receptor expression in acute myeloid leukemia (AML). We quantitatively examined the expression of interleukin-2 receptor α-chain (IL-2Rα, also known as CD25), IL-2Rβ, IL-3Rα, IL-4Rα, IL-5Rα, IL-6Rα, IL-7Rα, the common β-chain (βc), γc, granulocyte-macrophage colony-stimulating factor (GM-CSF)Rα, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 in leukemia cells from 767 adult patients with AML by flow cytometry and determined their prevalence and clinical significance. All cytokine receptors examined were expressed at varying levels, whereas the levels of IL-3Rα, GM-CSFRα, IL-2Rα, γc, c-kit, and G-CSFR exhibited a wide spectrum of ≥10,000 sites/cell. In terms of their French-American-British classification types, GM-CSFRα and c-fms were preferentially expressed in M4/M5 patients, G-CSF in M3 patients, and IL-2Rα in non-M3 patients. Elevated levels of IL-3Rα, GM-CSFRα, and IL-2Rα correlated with leukocytosis. In patients ≤60 years old, higher levels of these 3 receptors correlated with poor responses to conventional chemotherapy, but only IL-2Rα was associated with a shorter overall survival. By incorporating IL-2Rα status into cytogenetic risk stratification, we could sort out a significantly adverse-risk cohort from the cytogenetically intermediate-risk group. Analyses with various phenotypical risk markers revealed the expression of IL-2Rα as an independent prognostic indicator in patients with intermediate-risk cytogenetics. These findings were not observed in patients >60 years old. Our results indicate that several cytokine receptors were associated with certain cellular and clinical features, but IL-2Rα alone had prognostic value that provides an additional marker to improve current risk evaluation in AML patients ≤60 years old. PMID:26375984

  2. Evaluation of CD25-positive cells in relation to the subtypes and prognoses in various lymphoid tumours in dogs.

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    Mizutani, Noriyuki; Goto-Koshino, Yuko; Tsuboi, Masaya; Kagawa, Yumiko; Ohno, Koichi; Uchida, Kazuyuki; Tsujimoto, Hajime

    2016-05-01

    Interleukin-2 receptor alpha chain (CD25) expression has been reported in human lymphoid tumours and suggested to correlate with the prognosis. In this study, we detected CD25-positive cells in various types of lymphoid tumours in dogs. Immunohistochemical analyses of the tissues from diffuse large B-cell lymphoma (DLBCL) (n = 6), T-zone lymphoma (TZL) (n = 5), and follicular lymphoma (FL) (n = 2) revealed that cells strongly positive for CD25 were observed generally in accordance with lymphoma cell localization. CD25-positive cells were consistently detected in TZL and FL cases; however, the number of CD25-positive cells was variable among DLBCL cases. Furthermore, we evaluated the rate of CD25-positive cells by flow cytometric analysis in 29 dogs with lymphoid malignancies, including high-grade B-cell lymphoma (n = 17), TZL (n = 5), FL (n = 2), cutaneous lymphoma (n=2), and acute lymphoblastic leukaemia (ALL) (n = 3). CD25-positivity in the lymph node cells was significantly higher in dogs with high-grade B-cell lymphoma (mean ± SD, 49.6 ± 31.3%) or TZL (mean ± SD, 80.2 ± 10.0%) than that in healthy dogs (mean ± SD, 9.8 ± 2.8%). In prognostic analysis of 15 cases with high-grade B-cell lymphoma, the progression-free survival was significantly shorter in CD25-high group than that in CD25-low group. The results obtained in this study are useful for subtype differentiation and prognostic analysis of canine lymphomas and future development of molecular-targeted therapy directed at CD25.

  3. Depletion of CD25+ cells during acute toxoplasmosis does not significantly increase mortality in Swiss OF1 mice

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    Haroon Akbar

    2012-03-01

    Full Text Available The interleukin (IL-2R alpha chain (CD25 is expressed on regulatory T cells (Treg, which constitute more than 85% of the CD25+ T cell population in a naïve mouse. CD25 is also expressed on effector T cells in mice suffering from an acute infection by the obligate intracellular protozoan parasite, Toxoplasma gondii. Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice naturally susceptible to toxoplasmosis. The present study was done to explore the role of Treg cells using an anti-CD25 antibody-mediated depletion in mice naturally resistant to toxoplasmosis. Although a significant decrease in the percentage of Treg cells was observed following anti-CD25 monoclonal antibody injections, the depletion of CD25+ cells during acute toxoplasmosis did not significantly increase the mortality of Swiss OF1 mice and no significant difference was observed in the brain parasitic load between the mice in the depleted-infected and isotype-infected groups. We found no significant difference between the titres of total IgG in the sera of the mice from the two groups in the chronic phase. However, CD25+ cells depletion was followed by significantly higher levels of IL-12 in the serum of depleted mice than in that of mice injected with the isotype control antibody.

  4. EAE大鼠胸腺CD4+CD25+Foxp3+Treg细胞的动态变化及α-硫辛酸的干预作用%The variation of CD4+ CD25+ Foxp3+T regulative cells of thymus in different courses of EAE group and the effection of alpha lipoic acid

    Institute of Scientific and Technical Information of China (English)

    王燕燕; 蔺辉前; 檀国军; 郭书英; 张建娥

    2011-01-01

    目的 探讨实验性变态反应性脑脊髓炎(EAE)大鼠不同病程中胸腺CD4+ CD25+ Foxp3+Treg细胞变化情况及α-硫辛酸对EAE大鼠胸腺的干预作用.方法 取不同时期对照组、自然病程EAE组及α-硫辛酸EAE组大鼠的胸腺组织做流式细胞学,动态检测CD4+ CD25+ Foxp3+Treg细胞的变化情况.结果 EAE组大鼠急性期、复发期CD4+ CD25+ Foxp3+Treg细胞较同时期对照组明显减少(P 0. 05 ). Conclusion CD4 + CD25 + Foxp3 + Treg cells may play a role in the occurrence of EAE. There is significant relation between the development of EAE and CD4 + CD25 + Foxp3 + Treg cells. The function of ALA may not play through CD4 + CD25 + Foxp3 +Treg cells in immune adjustment at EAE. As the age added,the thymus may not be the main immune organ.

  5. Distinct roles for laminin globular domains in laminin alpha1 chain mediated rescue of murine laminin alpha2 chain deficiency.

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    Kinga I Gawlik

    Full Text Available BACKGROUND: Laminin alpha2 chain mutations cause congenital muscular dystrophy with dysmyelination neuropathy (MDC1A. Previously, we demonstrated that laminin alpha1 chain ameliorates the disease in mice. Dystroglycan and integrins are major laminin receptors. Unlike laminin alpha2 chain, alpha1 chain binds the receptors by separate domains; laminin globular (LG domains 4 and LG1-3, respectively. Thus, the laminin alpha1 chain is an excellent tool to distinguish between the roles of dystroglycan and integrins in the neuromuscular system. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide insights into the functions of laminin alpha1LG domains and the division of their roles in MDC1A pathogenesis and rescue. Overexpression of laminin alpha1 chain that lacks the dystroglycan binding LG4-5 domains in alpha2 chain deficient mice resulted in prolonged lifespan and improved health. Importantly, diaphragm and heart muscles were corrected, whereas limb muscles were dystrophic, indicating that different muscles have different requirements for LG4-5 domains. Furthermore, the regenerative capacity of the skeletal muscle did not depend on laminin alpha1LG4-5. However, this domain was crucial for preventing apoptosis in limb muscles, essential for myelination in peripheral nerve and important for basement membrane assembly. CONCLUSIONS/SIGNIFICANCE: These results show that laminin alpha1LG domains and consequently their receptors have disparate functions in the neuromuscular system. Understanding these interactions could contribute to design and optimization of future medical treatment for MDC1A patients.

  6. Anti-CD25 monoclonal antibody Fc variants differentially impact regulatory T cells and immune homeostasis.

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    Huss, David J; Pellerin, Alex F; Collette, Brian P; Kannan, Arun K; Peng, Liaomin; Datta, Abhishek; Wipke, Brian T; Fontenot, Jason D

    2016-07-01

    Interleukin-2 (IL-2) is a critical regulator of immune homeostasis through its non-redundant role in regulatory T (Treg) cell biology. There is major interest in therapeutic modulation of the IL-2 pathway to promote immune activation in the context of tumour immunotherapy or to enhance immune suppression in the context of transplantation, autoimmunity and inflammatory diseases. Antibody-mediated targeting of the high-affinity IL-2 receptor α chain (IL-2Rα or CD25) offers a direct mechanism to target IL-2 biology and is being actively explored in the clinic. In mouse models, the rat anti-mouse CD25 clone PC61 has been used extensively to investigate the biology of IL-2 and Treg cells; however, there has been controversy and conflicting data on the exact in vivo mechanistic function of PC61. Engineering antibodies to alter Fc/Fc receptor interactions can significantly alter their in vivo function. In this study, we re-engineered the heavy chain constant region of an anti-CD25 monoclonal antibody to generate variants with highly divergent Fc effector function. Using these anti-CD25 Fc variants in multiple mouse models, we investigated the in vivo impact of CD25 blockade versus depletion of CD25(+) Treg cells on immune homeostasis. We report that immune homeostasis can be maintained during CD25 blockade but aberrant T-cell activation prevails when CD25(+) Treg cells are actively depleted. These results clarify the impact of PC61 on Treg cell biology and reveal an important distinction between CD25 blockade and depletion of CD25(+) Treg cells. These findings should inform therapeutic manipulation of the IL-2 pathway by targeting the high-affinity IL-2R. PMID:27012310

  7. RA8, A human anti-CD25 antibody against human treg cells

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    Arias, Robyn; Flanagan, Meg; Miller, Keith D.; Nien, Yu-Chih; Hu, Peisheng; Gray, Dixon; Khawli, Leslie A.; Epstein, Alan L.

    2007-06-01

    Although anti-CD25 antibodies exist for clinical use in patients, there is a need for the development of a human Treg antibody that will abrogate the immunosuppressive function of this small but critical T cell subtype. Based upon mounting evidence that the level of Treg cells in the tumor microenvironment correlates with clinical prognosis and stage in man, it appears that Treg cells play an important role in the tumor's ability to overcome host immune responses. In mice, the rat anti-mouse CD25 antibody PC61 causes depletion of CD25-bearing Treg cells both peripherally in lymphatic tissues and in the tumor microenvironment, without inducing symptoms of autoimmunity. A similar antibody, though with the ability to delete Treg cells specifically, would be an important new tool for reversing tumor escape associated with Treg immunosuppression in man. To begin to generate such a reagent, we now describe the development of a human anti-CD25 antibody using a novel yeast display library. The target antigen CD25-Fc was constructed and used for five rounds of selection using a non-immune yeast display library that contained as many as 109 single chain variable fragments (scFv). Two unique clones with low KD values (RA4 and RA8) were then selected to construct fully human anti-CD25 antibodies (IgG1/kappa) for stable expression. One antibody, RA8, showed excellent binding to human CD25+ cell lines and to human Treg cells and appears to be an excellent candidate for the generation of a human reagent that may be used in man for the immunotherapy of cancer.

  8. Theoretical Study on Alpha-Decay Chains of 294117 and 293117

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    SHENG Zong-Qiang; REN Zhong-Zhou

    2011-01-01

    The newly synthesized element 117 and its alpha-decay chains are systematically investigated in the framework of the relativistic mean field theory with parameter sets NL-Z2 and TMA.The ground-state properties of the superheavy nuclei on the alpha-decay chains of 294117 and 293117 are calculated.The experimental alpha-decay energies and half-lives of the two alpha-decay chains are reasonably reproduced by the model The detailed discussions on the binding energies, alpha-decay energies, half-lives, quadrupole deformations, potential energy curves, and single particle levels of the two alpha-decay chains are made.

  9. Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

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    Forward, Nicholas A.; Conrad, David M. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Power Coombs, Melanie R.; Doucette, Carolyn D. [Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Furlong, Suzanne J. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Lin, Tong-Jun [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia (Canada); Hoskin, David W., E-mail: d.w.hoskin@dal.ca [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Surgery, Dalhousie University, Halifax, Nova Scotia (Canada)

    2011-04-22

    Highlights: {yields} Curcumin inhibits CD4{sup +} T-lymphocyte proliferation. {yields} Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4{sup +} T-lymphocytes. {yields} Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. {yields} IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4{sup +} T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 ({alpha} chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca{sup 2+} release to inhibit I{kappa}B phosphorylation, which is required for nuclear translocation of the transcription factor NF{kappa}B. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4{sup +}CD25{sup +} regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

  10. The proportion of hybrid heterodimers in homozygous or doubly heterozygous beta chain variant hemoglobinopathies associated with alpha chain hemoglobin variants.

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    Krauss, J S

    2000-10-01

    Four alpha genes exist on chromosome 16, but one or more of these genes can be deleted in association with Hemoglobin (Hb)G-Philadelphia in cis to alpha-thalassemia-2 in African-Americans. Therefore, the proportion of HbG-Philadelphia in HbG heterozygotes is trimodal at about 25% for alphaGalpha/alpha alpha, 33% for alphaG-/alpha alpha, and 50% for alphaG-/alpha alpha in patients with HbA. Those who are homozygous or doubly heterozygous for beta chain variants (betaX2 or betaXbetaY) have neither HbA nor the alpha chain variant (alphaX2 betaA2), but have hybrid heterodimers (alphaX2 betaX2). The proportion of hybrid heterodimers here should also be trimodal mirroring alpha gene status. Eleven patients were identified: 4 with Hb SSG, 3 with Hb SCG, and 1 each with Hb OCG, HbSSMontgomery, HbSSChicago, and HbSSBourmedes. Heterodimer proportions were: 43.3 +/- 1.5, 33.5 +/- 2.3, and 15.8 +/- 1.1% for 2, 3, and 4 respective alpha genes which had been studied in 8/11 of the patients (r = 0.98), implying that the prime determinant of the proportion of hybrid heterodimers in this patient group is the number of functional alpha genes. PMID:11045763

  11. The complete cDNA sequence of laminin alpha 4 and its relationship to the other human laminin alpha chains.

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    Richards, A; Al-Imara, L; Pope, F M

    1996-06-15

    We previously localised the gene (LAMA4) encoding a novel laminin alpha 4 chain to chromosome 6q21. In this study, we describe the complete coding sequence and compare the protein with the other three known human laminin alpha chains. Although closely linked to LAMA2, the LAMA4 product most closely resembles laminin alpha 3, a constituent of laminin 5. Like laminin alpha 3A, the alpha 4 chain is a truncated version of the alpha 1 and alpha 2 chains, with a much reduced short arm. While the alpha 4 molecule is most similar to alpha 3, it shares some features of the C-terminal domains G4 and G5 in common with alpha 2. Unlike the LAMA3 gene, LAMA4 appears to encode only a single transcript, as determined by 5' rapid amplification of cDNA ends. The cDNA sequence encodes 1816 amino acids, which include a 24-residue signal peptide. The gene is expressed in skin, placenta, heart, lung, skeletal muscle, and pancreas. We have also shown that the mRNA can be readily reverse transcribed and amplified from cultured dermal fibroblasts. PMID:8706685

  12. Biological features of intrahepatic CD4+CD25+ T cells in the naturally tolerance of rat liver transplantation

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    LU Ling; ZHANG Feng; PU Liyong; YAO Aihua; YU Yue; SUN Beicheng; LI Guoqiang

    2007-01-01

    The biological features of intrahepatic CD4+CD25+ T regulatory cells in the naturally tolerance of rat liver transplantation were explored.Orthotopic liver transplantation was performed in two allogeneic rat strain combinations,one with fatal immunosuppression despite a complete major histocompatibility complex mismatch.The subjects were divided into three groups according to different donors and recipients [Tolerance group:LEW-to-DA;Rejection group:DA-to-LEW;Syngegnic group(control group):DAto-DA].The proportion of intrahepatic CD4+CD25+ T cells from three groups was determined by flow cytometry(FCM)in different time.The intrahepaitc CD4+CD25+ T cells were isolated by magnetic activated cell sorting(MACS)method and identified by FCM.The Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction(RT-PCR).And their suppression on the proliferation of CD4+CD25- T effector cells was analyzed by cell proliferation assay in vitro.Beginning immediately after transplantation,the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection group.The proportion of Treg cells declined after day 5,and such reduction was more dramatic in the Rejection group than in the Tolerance group.Animals in the Tolerance group showed a second increase in the proportion after day 14.Intrahepatic CD4+CD25+T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte reaction.The purity of CD4+CD25+ T cells sorted by MACS was 86%-93%.The CD4+CD25+ T cells could specifically express the Foxp3 gene compared with CD4+CD25- T cells.In vitro,the spleen cells from LEW rats can irritate the proliferation of CD4+CD25+ T cells more obviously than the syngegnic spleen cells.CD4+CD25+ Tr cells could suppress the proliferation of CD4+CD25- T cells,but the inhibition was reversed by exogenous IL-2(200 U/mL).The CD4+CD25+ T regulatory cells specifically express the Foxp3 gene,which may play an

  13. Structure and diversity of the TCR alpha-chain in a teleost fish.

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    Partula, S; de Guerra, A; Fellah, J S; Charlemagne, J

    1996-07-01

    T cell receptor beta-chain genes are well characterized in representatives of most vertebrate phyla, from sharks to mammals, but the molecular structure of complete TCR alpha-chains has not yet been established in cold-blooded vertebrates. We used a PCR approach to isolate cDNAs encoding putative teleost fish (Oncorhynchus mykiss, rainbow trout) TCR alpha-chains. Eight V alpha segments were identified, belonging to six different families, and the best amino acid sequence identity scores for these trout V alpha were all provided by mammalian V alpha or V delta sequences. Twenty-four (60.1 %) of the 39 analyzed V alpha segments belong to the V alpha 2 family, which has limited homology with mammalian V alpha/delta sequences and with the human V pre-B sequence. A total of 32 different J alpha segments were identified from 40 J alpha regions sequenced, suggesting that a large repertoire of J alpha segments is a characteristic of most vertebrates. The structural properties of the TCR alpha-chain complementarity-determining region 3 loop are well conserved between trout and mammals, suggesting that this region has been under continuous selective pressure in jawed vertebrate evolution. The trout C alpha segment has conserved N-terminal and transmembrane domains, but the C alpha intercysteine distance contains only 40 residues, significantly smaller as compared with mammals (49-56 residues). The conserved features of teleost fish TCR beta- and alpha-chains with their mammalian equivalents suggest that TCR-alpha beta receptors were still present in the common Devonian ancestors of modern teleost fish and mammals, about 450 million years ago. PMID:8683116

  14. Molecular characterization of hemoglobin alpha-D chains from Geochelone carbonaria and Geochelone denticulata land turtles.

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    Melo, Mônica B; Bordin, Silvana; Duarte, Adriana S S; Ogo, Satie H; Torsoni, Márcio A; Saad, Sara T O; Costa, Fernando F

    2003-02-01

    In order to help elucidate the evolution of alpha-globins, the complete cDNA and amino acid sequences of Geochelone carbonaria and Geochelone denticulata land turtles alpha-D chains have been described. In G. carbonaria, the cDNA is 539 bp with ATG start codon located at position 46, TGA stop codon at position 469 and AATAAA polyadenylation signal at position 520. In G. denticulata, the cDNA is 536 bp with ATG start codon located at position 46, TGA stop codon at position 469 and AATAAA polyadenylation signal at position 517. Both cDNAs codify 141 amino acid residues, differing from each other in only four amino acid residues. When comparing with human Hb alpha-chain, alterations in important regions can be noted: alpha110 Ala-Gly, alpha114 Pro-Gly, alpha117 Phe-Tyr and alpha122 His-Gln. There is a high homology between the amino acids of these turtles when compared with chicken alpha-D chains, progressively decreasing when compared with human, crocodile, snake, frog and fish alpha-chains. Phylogenetic analysis of alpha-D chains shows that those of turtles are closer to those of birds than to snakes and lizards. PMID:12568815

  15. Association Between Circulating Early Endothelial Progenitors and CD4+CD25+ Regulatory T Cells: A Possible Cross-talk between Immunity and Angiogenesis?

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    Shmuel Schwartzenberg

    2005-01-01

    Full Text Available Regulatory T-cells (Treg are a recently defined subset of CD4+ cells that can suppress inflammation and induce tolerance. Phenotypically, T-regs are characterized by a high level of expression of the IL-2 receptor alpha chain, CD25. Endothelial progenitor cells (EPCs can transform into mature endothelial cells and promote vessel formation by inducing postnatal angiogenesis and vasculogenesis. Herein, we tested the hypothesis that an association exists between circulating EPC and Tregs that could potentially allude to cross talk between immunity and angiogenesis. Peripheral blood mononuclear cells were isolated by Ficoll density-gradient centrifugation from 28 subjects. Circulating number of EPCs at various developmental stages (CD133+CD34+, CD133+VEGFR2+, CD34+VEGFR2+, total CD4+ and Treg CD4+CD25high numbers were determined by FACS analysis. We found a positive correlation between early progenitor cell (CD133+CD34+ number and Tregs, but no correlation between differentiated EPCs and Tregs, or between CD4+ and any of the EPCs sampled. Early EPCs (CD133+CD34+ did not correlate with CD34+/KDR or with CD133/KDR cells. Circulating numbers of early but not ‘mature’ EPC correlate with Tregs but not CD4 numbers. This finding may suggest a novel role for Tregs in promoting EPC recruitment or delaying EPC maturation.

  16. Depletion of CD4+CD25+ regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma

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    Yi-Ling Chen; Jung-Hua Fang; Ming-Derg Lai; Yan-Shen Shan

    2008-01-01

    AIM: To elucidate the distribution of CD4+CD25+ regulatory T cells (Tregs) in different lymphoid tissues and its local enhancement on tumor growth before and after depletion of CD4+CD25+ Tregs.METHODS: Female ICR mice were gavaged with benzo[a]pyrene (BaP) to induce forestomach carcinoma. CD4+CD25+ Tregs were intraperitoneally depleted with monoclonal antibody PC61. These mice were divided into BaP-only, BaP+IgG, BaP+PC61, and control groups. The forestomach of mice was dissected for histological analysis, and tunnel test was performed for apoptosis of tumor cells. CD4+CD25+ Tregs were sorted from different lymphoid tissues and expression of Foxp3, IL-10, and chemokine receptors was analyzed by flow cytometry, semi-quantitative and real-time polymerase chain reaction.RESULTS: The mice gavaged with only BaP showed increased forestomach papilloma and carcinoma at wk 16 and 32. The proportion of CD4+CD25+ Tregs was significantly higher in peri-stomach regional lymph nodes than in other lymphoid tissues. These CD4+CD25+ Tregs in regional lymph nodes expressed higher levels of Foxp3 and IL-10, enriched in the CD62L-subset, and CCR1 and CCR5 chemokine receptors. In mice gavaged with BaP+PC61, the number of tumor nodules and tumor volume decreased significantly with massive infiltrating cells and apoptosis of tumor cells. In the draining regional lymph nodes, the number of CD4+CD25+ Tregs also decreased significantly.CONCLUSION: Inducible and activated CD4+CD25+ Tregs in the draining regional lymph nodes suppress host local immunity during tumor growth. Depletion of CD4+CD25+ Tregs can promote host local immunity to suppress tumor growth.

  17. Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling.

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    Zanin-Zhorov, Alexandra; Cahalon, Liora; Tal, Guy; Margalit, Raanan; Lider, Ofer; Cohen, Irun R

    2006-07-01

    CD4+CD25+ Tregs regulate immunity, but little is known about their own regulation. We now report that the human 60-kDa heat shock protein (HSP60) acts as a costimulator of human Tregs, both CD4+CD25int and CD4+CD25hi. Treatment of Tregs with HSP60, or its peptide p277, before anti-CD3 activation significantly enhanced the ability of relatively low concentrations of the Tregs to downregulate CD4+CD25- or CD8+ target T cells, detected as inhibition of target T cell proliferation and IFN-gamma and TNF-alpha secretion. The enhancing effects of HSP60 costimulation on Tregs involved innate signaling via TLR2, led to activation of PKC, PI3K, and p38, and were further enhanced by inhibition of ERK. HSP60-treated Tregs suppressed target T cells both by cell-to-cell contact and by secretion of TGF-beta and IL-10. In addition, the expression of ERK, NF-kappaB, and T-bet by downregulated target T cells was inhibited. Thus, HSP60, a self-molecule, can downregulate adaptive immune responses by upregulating Tregs innately through TLR2 signaling. PMID:16767222

  18. The laminin alpha chains: expression, developmental transitions, and chromosomal locations of alpha1-5, identification of heterotrimeric laminins 8-11, and cloning of a novel alpha3 isoform.

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    Miner, J H; Patton, B L; Lentz, S I; Gilbert, D J; Snider, W D; Jenkins, N A; Copeland, N G; Sanes, J R

    1997-05-01

    Laminin trimers composed of alpha, beta, and gamma chains are major components of basal laminae (BLs) throughout the body. To date, three alpha chains (alpha1-3) have been shown to assemble into at least seven heterotrimers (called laminins 1-7). Genes encoding two additional alpha chains (alpha4 and alpha5) have been cloned, but little is known about their expression, and their protein products have not been identified. Here we generated antisera to recombinant alpha4 and alpha5 and used them to identify authentic proteins in tissue extracts. Immunoprecipitation and immunoblotting showed that alpha4 and alpha5 assemble into four novel laminin heterotrimers (laminins 8-11: alpha4beta1gamma1, alpha4beta2gamma1, alpha5beta1gamma1, and alpha5beta2gamma1, respectively). Using a panel of nucleotide and antibody probes, we surveyed the expression of alpha1-5 in murine tissues. All five chains were expressed in both embryos and adults, but each was distributed in a distinct pattern at both RNA and protein levels. Overall, alpha4 and alpha5 exhibited the broadest patterns of expression, while expression of alpha1 was the most restricted. Immunohistochemical analysis of kidney, lung, and heart showed that the alpha chains were confined to extracellular matrix and, with few exceptions, to BLs. All developing and adult BLs examined contained at least one alpha chain, all alpha chains were present in multiple BLs, and some BLs contained two or three alpha chains. Detailed analysis of developing kidney revealed that some individual BLs, including those of the tubule and glomerulus, changed in laminin chain composition as they matured, expressing up to three different alpha chains and two different beta chains in an elaborate and dynamic progression. Interspecific backcross mapping of the five alpha chain genes revealed that they are distributed on four mouse chromosomes. Finally, we identified a novel full-length alpha3 isoform encoded by the Lama3 gene, which was previously

  19. Influence of membrane CD25 stability on T lymphocyte activity: implications for immunoregulation.

    Directory of Open Access Journals (Sweden)

    Todd M Brusko

    Full Text Available BACKGROUND: CD25, a component of the IL-2 receptor, is important in T cell proliferation, activation induced cell death, as well as the actions of both regulatory (Treg and effector (Teff T cells. Recent genome wide association studies have implicated the CD25 locus as an important region for genetic susceptibility to a number of autoimmune disorders, with serum levels of soluble CD25 receptor (sCD25 serving as a potential phenotypic marker for this association. However, the functional impact of CD25 cleavage, as well as the influence of sCD25 on immunoregulatory activities, remain largely unknown and form the basis of this effort. METHODOLOGY/PRINCIPAL FINDINGS: The generation of sCD25 by Treg (CD4(+CD25(+ and Teff (CD4(+CD25(- cells was examined during in vitro suppression assays, efforts that demonstrated constitutive and stable surface CD25 expression on Treg throughout the period of in vitro assessment. In contrast, Teff cells increased CD25 expression during the process of in vitro suppression, with supernatant sCD25 levels correlating to the amount of cellular proliferation. Interestingly, under serum-free conditions, Tregs partially lost their characteristic anergic and suppressive properties. sCD25 supplementation at physiological concentrations to serum free in vitro suppression assays reduced Teff proliferation without specifically influencing suppression. Indeed, sCD25 production within these cultures correlated with cell death. CONCLUSIONS/SIGNIFICANCE: These results support the notion that sCD25 functions as both a surrogate marker of T cell activation as well as an indicator of subsequent cellular death. In addition, the role of CD25 in immunomodulation is likely dependent on the local inflammatory milieu, with molecules capable of modulating surface CD25 expression playing a key role in defining immune responsiveness.

  20. Salt bridge residues between I-Ak dimer of dimers alpha-chains modulate antigen presentation.

    Science.gov (United States)

    Yadati, S; Nydam, T; Demian, D; Wade, T K; Gabriel, J L; Barisas, B G; Wade, W F

    1999-03-15

    Class II dimers of dimers are predicted to have functional significance in antigen presentation. The putative contact amino acids of the I-Ak class II dimer of dimers have been identified by molecular modeling based on the DR1 crystal structure (Nydam et al., Int. Immunol. 10, 1237,1998). We have previously reported the role in antigen presentation of dimer of dimers contact amino acids located in the C-terminal domains of the alpha- and beta-chains of class II. Our calculations show that residues Ealpha89 and Ralpha145 in the alpha2-domain form an inter alpha-chain salt bridge between pairs of alphabeta-heterodimers. Other residues, Qalpha92 and Nalpha115, may be involved in close association in that part of the alpha-chain. We investigated the role of these amino acids on class II expression and antigen presentation. Class II composed of an Ealpha89K substituted alpha-chain paired with a wt beta-chain exhibited inhibited antigen presentation and expression of alpha-chain serologic epitopes. In contrast, mutation of Ralpha145E had less affect on antigen presentation and did not affect I-Ak serologic epitopes. Interchanging charges of the salt bridge residues by expressing both Ralpha145E and Ealpha89K on the same chain obviated the large negative effect of the Ealpha89K mutation on antigen presentation but not on the serologic epitopes. Our results are similar for those reported for mutation of DR3's inter-chain salt bridge with the exception that double mutants did not moderate the DR3 defect. Interestingly, the amino acids differences between I-A and DR change the location of the inter-chain salt bridges. In DR1 these residues are located at positions Ealpha88 and Kalpha111; in I-Ak these residues are located at position Ealpha89 and Ralpha145. Inter alpha-chain salt bridges are thus maintained in various class II molecules by amino acids located in different parts of the alpha2-domain. This conservation of structure suggests that considerable functional

  1. Intestinal lamina propria retaining CD4+CD25+ regulatory T cells is a suppressive site of intestinal inflammation.

    Science.gov (United States)

    Makita, Shin; Kanai, Takanori; Nemoto, Yasuhiro; Totsuka, Teruji; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Yamamoto, Masafumi; Kiyono, Hiroshi; Watanabe, Mamoru

    2007-04-15

    It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only does active suppression by regulatory T (T(REG)) cells play an important role in the normal intestinal homeostasis, but also that its dysregulation of immune response leads to the development of inflammatory bowel disease. In this study, we demonstrate that murine CD4(+)CD25(+) T cells residing in the intestinal lamina propria (LP) constitutively express CTLA-4, glucocorticoid-induced TNFR, and Foxp3 and suppress proliferation of responder CD4(+) T cells in vitro. Furthermore, cotransfer of intestinal LP CD4(+)CD25(+) T cells prevents the development of chronic colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells into SCID mice. When lymphotoxin (LT)alpha-deficient intercrossed Rag2 double knockout mice (LTalpha(-/-) x Rag2(-/-)), which lack mesenteric lymph nodes and Peyer's patches, are transferred with CD4(+)CD45RB(high) T cells, they develop severe wasting disease and chronic colitis despite the delayed kinetics as compared with the control LTalpha(+/+) x Rag2(-/-) mice transferred with CD4(+)CD45RB(high) T cells. Of note, when a mixture of splenic CD4(+)CD25(+) T(REG) cells and CD4(+)CD45RB(high) T cells are transferred into LTalpha(-/-) x Rag2(-/-) recipients, CD4(+)CD25(+) T(REG) cells migrate into the colon and prevent the development of colitis in LTalpha(-/-) x Rag2(-/-) recipients as well as in the control LTalpha(+/+) x Rag2(-/-) recipients. These results suggest that the intestinal LP harboring CD4(+)CD25(+) T(REG) cells contributes to the intestinal immune suppression. PMID:17404275

  2. cDNA clone for the alpha-chain of human beta-hexosaminidase: deficiency of alpha-chain mRNA in Ashkenazi Tay-Sachs fibroblasts.

    OpenAIRE

    Myerowitz, R; Proia, R L

    1984-01-01

    We have isolated a cDNA clone containing sequences complementary to mRNA encoding the alpha-chain of the lysosomal enzyme beta-hexosaminidase. RNA from a human lung fibroblast strain, IMR90, was enriched for beta-hexosaminidase messenger by polysome immunoselection with antiserum against beta-hexosaminidase A. This preparation was used to construct cDNA recombinant plasmids by the Okayama-Berg vector primer procedure. After transformation of Escherichia coli, 385 ampicillin-resistant colonies...

  3. Physiological covalent regulation of rat liver branched-chain alpha-ketoacid dehydrogenase

    International Nuclear Information System (INIS)

    A radiochemical assay was developed for measuring branched-chain alpha-ketoacid dehydrogenase activity of Triton X-100 extracts of freeze-clamped rat liver. The proportion of active (dephosphorylated) enzyme was determined by measuring enzyme activities before and after activation of the complex with a broad-specificity phosphoprotein phosphatase. Hepatic branched-chain alpha-ketoacid dehydrogenase activity in normal male Wistar rats was 97% active but decreased to 33% active after 2 days on low-protein (8%) diet and to 13% active after 4 days on the same diet. Restricting protein intake of lean and obese female Zucker rats also caused inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex. Essentially all of the enzyme was in the active state in rats maintained for 14 days on either 30 or 50% protein diets. This was also the case for rats maintained on a commercial chow diet (minimum 23% protein). However, maintaining rats on 20, 8, and 0% protein diets decreased the percentage of the active form of the enzyme to 58, 10, and 7% of the total, respectively. Fasting of chow-fed rats for 48 h had no effect on the activity state of hepatic branched-chain alpha-ketoacid dehydrogenase, i.e., 93% of the enzyme remained in the active state compared to 97% for chow-fed rats. However, hepatic enzyme of rats maintained on 8% protein diet was 10% active before starvation and 83% active after 2 days of starvation. Thus, dietary protein deficiency results in inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex, presumably as a consequence of low hepatic levels of branched-chain alpha-ketoacids

  4. Deletional rearrangement in the human T-cell receptor. cap alpha. -chain locus

    Energy Technology Data Exchange (ETDEWEB)

    de Villartay, J.P.; Lewis, D.; Hockett, R.; Waldmann, T.A.; Korsmeyer, S.J.; Cohen, D.I.

    1987-12-01

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed ..cap alpha.. and ..beta... In the course of characterizing human T-cell tumors with an immature (CD4/sup -/, CD8/sup -/) surface phenotype, the authors detected a 2-kilobase ..cap alpha..-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early ..cap alpha..) located between the ..cap alpha..-chain variable- and joining-region genes had been spliced to the ..cap alpha.. constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the ..cap alpha.. gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature ..cap alpha.. gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the ..gamma..delta heterodimeric receptor and is deleted from mature (..cap alpha beta..-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (..gamma..delta-expressing) T cells and mature (..cap alpha beta..-expressing) T cells.

  5. CD4+CD25+CD127low regulatory T cells play predominant anti-tumor suppressive role in hepatitis B virus associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Shreya eSharma

    2015-02-01

    Full Text Available Background:Hepatocellular carcinoma (HCC is the second leading cause of cancer death worldwide and hepatitis B is one of the commonest causes. T regulatory cells (Tregs are strong immunomodulators and are likely to play a major role in HCC development. HBV infection is reported to induce expansion of Tregs. We investigated the CD4+CD25+CD127-veFoxP3+ Tregs in HBV related HCC as compared to non-HBV-HCC. Patients and Methods: Whole blood Immunophenotyping was analysed by multicolor flow cytometry in patients with HBV related HCC (HBV-HCC, n=17, non-HBV-HCC (n=22; NASH =16, alcohol related=6 and chronic hepatitis B infection (CHBV; n=10.T regulatory cells and functionality was checked by in vitro suppression assays using CD4+ CD25+ CD127low T regulatory cells. Levels of serum alpha fetoprotein(AFP,expression of FoxP3, IL-10, PD-1, TGF-β and Notch in Tregs and liver explants was analyzed by flow cytometry, immuno-histochemistry and quantitative RT-PCR.Results:CD4+CD25+hi and Foxp3 expression in CD4+CD25+hiCD127low was significantly increased (P=0.04, P=0.007 in HBVHCC compared to non-HBVHCC and CHBV patients. HBVHCC also showed high IL-10and TGF-β secreting CD4+CD25+hiTregs.The PD1 expression in CD4+CD25+hi was significantly decreased in the HBVHCC than non-HBVHCC. In HBVHCC, AFP levels were significantly high (median 941, range 2-727940 than non-HBVHCC (median 13.5, range 2-18,900. In HBVHCC,patients with high AFP (range;3982-727940 ng/ml showed positive correlation with Foxp3 expression in CD4+CD25+hi CD127low(r=0.857,p=0.014. Reduced PD1 expression in HBVHCC also had negative correlation with FOXP3 in CD4+CD25+hi CD127low(r=-0.78, p=0.04. However, AFP levels in non-HBVHCC showed negative correlation with (R=-0.67, p=0.005 with CD4+CD25+hi Tregs. Conclusions:Our results demonstrates that CD4+ CD25+hi Tregs from HBVHCC patients have decreased expression of PD-1, resulting in higher IL-10 and TGF-β secretion. Increased suppressive ability of

  6. Synthesis of Long Chain Unsaturated-alpha,omega-Dicarboxylic Acids from Renewable Materials via Olefin Metathesis

    Science.gov (United States)

    The self-metathesis reaction of soy, rapeseed, tall, and linseed oil fatty acids was investigated for the synthesis of symmetrical long-chain unsaturated-alpha,omega-dicarboxylic acids. The metathesis reactions were carried out in the presence of a Grubbs catalyst under solvent-free conditions at a...

  7. Expression of interleukin-2R alpha and interleukin-2R beta in Hodgkin's disease.

    OpenAIRE

    Tesch, H.; A. Günther; Abts, H.; Jücker, M; Klein, S; Krueger, G. R.; Diehl, V.

    1993-01-01

    Hodgkin and Reed-Sternberg cells, the putative malignant cells of Hodgkin's disease (HD), carry regularly the CD25 antigen that forms one chain of the interleukin-2 (IL-2) receptor (IL-2R alpha). To analyze the putative role of IL-2R expression in Hodgkin's disease, we have investigated the expression of both IL-2R alpha and IL-2R beta chains in HD-derived cell lines and in primary specimens from patients with HD. Expression of IL-2R alpha and IL-2R beta was detected in all HD-derived cell li...

  8. CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells.

    Science.gov (United States)

    Makita, Shin; Kanai, Takanori; Oshima, Shigeru; Uraushihara, Koji; Totsuka, Teruji; Sawada, Taisuke; Nakamura, Tetsuya; Koganei, Kazutaka; Fukushima, Tsuneo; Watanabe, Mamoru

    2004-09-01

    It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only active suppression by regulatory T cells plays an important role in the normal intestinal homeostasis, but also its dysregulation leads to the development of inflammatory bowel disease. In this study, we demonstrate that the CD4(+)CD25(bright) T cells reside in the human intestinal lamina propria (LP) and functionally retain regulatory activities. All human LP CD4(+) T cells regardless of CD25 expression constitutively expressed CTLA-4, glucocorticoid-induced TNFR family-related protein, and Foxp3 and proliferate poorly. Although LP CD4(+)CD25(-) T cells showed an activated and anergic/memory phenotype, they did not retain regulatory activity. In LP CD4(+)CD25(+) T cells, however, cells expressing CD25 at high levels (CD4(+)CD25(bright)) suppressed the proliferation and various cytokine productions of CD4(+)CD25(-) T cells. LP CD4(+)CD25(bright) T cells by themselves produced fewer amounts of IL-2, IFN-gamma, and IL-10. Interestingly, LP CD4(+)CD25(bright) T cells with regulatory T activity were significantly increased in patients with active inflammatory bowel disease. These results suggest that CD4(+)CD25(bright) T cells found in the normal and inflamed intestinal mucosa selectively inhibit the host immune response and therefore may contribute to the intestinal immune homeostasis. PMID:15322172

  9. Impairment of circulating CD4+CD25+ regulatory T cells in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Chi, Li-Jun; Wang, Hua-Bing; Wang, Wei-Zhi

    2008-03-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated peripheral nervous system disease. CD4+CD25+ T regulatory cells (Tregs) have been unequivocally shown to be critical in maintaining immune tolerance and preventing auto-immune diseases by suppressing self-reactive T cells. Thus, we hypothesized that the numbers and/or the function of Tregs would be deranged during the progressive or relapse phases of CIDP. The number of Tregs was determined by flow cytometry according to their characteristic CD4+CD25(high) membrane phenotype. Functional characterization of Tregs was analyzed by suppression of proliferation and secretion of cytokines by co-cultured effector CD4+CD25- T cells. FOXP3 message expression level was assessed by quantitative real-time polymerase chain reaction. The results showed significant reduction in both the number and the suppressive function of Tregs in the patients with CIDP compared with healthy controls. Also, Tregs isolated from CIDP patients expressed lower levels of FoxP3 mRNA. During the progressive or the relapsing phases of CIDP, the number of Tregs was reduced, and the suppressive function of them decreased. These findings may be helpful to our understanding of the possible role of Tregs in the pathogenesis of CIDP.

  10. Exploration of the Partial Different Roles of CD4 + CD25 + Tregs and CD4 + CD25HighTregs in Sero-resistance Syphilitic Patients%梅毒血清固定患者CD4+CD25+Treg细胞和CD4+CD25High Treg细胞功能的差异探讨

    Institute of Scientific and Technical Information of China (English)

    张明海; 赵建斌

    2013-01-01

    目的 探讨梅毒血清固定患者外周血CD4+ CD25+ Treg细胞和CD4+ CD25HighTreg细胞功能是否发生变化.方法 采用流式细胞术(FCM)检测28例梅毒血清固定患者和28例梅毒转阴患者外周血CD4+CD25+ Treg细胞和CD4+ CD25High Treg细胞中FOXP3和CTLA-4的水平;采用免疫磁珠细胞分选技术(MACS)和Realtime-PCR技术检测CD4+ CD25+ Treg细胞的FOXP3和CTLA-4mRNA水平.结果 梅毒血清固定组外周血CD4+ CD25+Treg细胞功能增强,而梅毒血清转阴组外周血CD4+ CD25HighTreg细胞功能稳定.结论 CD4+CD25+Treg和CD4+ CD25HighTreg细胞在梅毒血清固定形成中作用的方式或途径存在部分差异.

  11. Evaluation of CD4+CD25+ regulatory T cells in patients with hepatocellular carcinoma and liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Amal Abdel Aleem, ** Eman A Abdel Rahman and ***Abdel Aty M. Elgonimy

    2011-04-01

    Full Text Available The emergence of a Tumor results from the disruption of cell growth regulation as well as from failure of the host to provoke a sufficient immunological anti-tumor response. Regulatory T cells CD4+CD25+ (Tregs play an important role in maintaining peripheral self-tolerance, thus preventing autoimmune pathologies. However, in certain situations Tregs can impair effective immunity to some pathogens and tumor cells. Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related death in the world, and in developed countries it is expected to continue to increase because of the epidemic of chronic hepatitis C virus (HCV infection. Previous studies also showed that Tregs infiltrating HCC tumors were an indicator of poor prognosis. Aim: of this study was to evaluate CD4+CD25+ Treg cells in patients with HCC and liver cirrhosis and their correlation with liver tumor markers and grading. Patients and Methods: The study included 30 patients, 15 patients had HCC (group I and 15 were cirrhotic patients (group II. In addition, 10 healthy subjects were used as controls. All patients were subjected to clinical examination and laboratory investigations including liver function tests, hepatitis B markers (HBs Ag, HBeAg and HBc-Ab and HCV antibodies were detected by ELISA. and Bilharzial Abs by indirect hemagglutination test. CD4+CD25+ Tcells were quantified in the blood by flow cytometry, alpha feto protein by Cobas e 411, To evaluate HCC grading ,abdominal sonography, C.T.and liver biopsy were done. Patients were categorized into mildely differentiated (grad 1, moderately differentiated (grad 11 and poorly differentiated (grad 111. Results: There were significant increased in serum AFP, and CD4+CD25+% in patients with HCC, and in patients with liver cirrhosis when compared to control group (p<0.05, and highly significant increased in AFP, and CD4+CD25+ % in patients with HCC when compared to patients with liver cirrhosis (p<0.001. In HCC patients

  12. Random length assortment of human and mouse T cell receptor for antigen alpha and beta chain CDR3.

    Science.gov (United States)

    Johnson, G; Wu, T T

    1999-10-01

    In view of the recently determined three-dimensional structures of complexes formed by the T cell receptor for antigen (TCR), the processed peptide and the MHC class I molecule, it is expected that the combined configuration formed by the third complementarity determining regions (CDR3) of TCR alpha and beta chains will be very restricted in size and shape due to the limited length variations of the processed peptides. Thus, the combined TCR alpha and beta chain CDR3 lengths should have a fairly narrow distribution. This feature can be due to the selective association of long alpha chain CDR3 with short beta chain CDR3 and vice versa or due to random assortment of alpha and beta chain CDR3 of even narrower length distribution. Based on existing translated amino acid sequence data, it has been found that the latter mechanism is responsible.

  13. Structure and diversity of the T-cell receptor alpha chain in the Mexican axolotl.

    Science.gov (United States)

    Fellah, J S; Kerfourn, F; Dumay, A M; Aubet, G; Charlemagne, J

    1997-01-01

    Polymerase chain reaction was used to isolate cDNA clones encoding putative T-cell receptor (TCR) alpha chains in an amphibian, the Mexican axolotl (Ambystoma mexicanum). Five TCRalpha-V chain-encoding segments were identified, each belonging to a separate family. The best identity scores for these axolotl TCRalpha-V segments were all provided by sequences belonging to the human TCRalpha-V1 family and the mouse TCRalpha-V3 and TCRalpha-V8 families. A total of 14 different TCRA-J segments were identified from 44 TCRA-V/TCRA-J regions sequenced, suggesting that a large repertoire of TCRA-J segments is a characteristic of most vertebrates. The structure of the axolotl CDR3 alpha chain loop is in good agreement with that of mammals, including a majority of small hydrophobic residues at position 92 and of charged, hydrophilic, or polar residues at positions 93 and 94, which are highly variable and correspond to the TCRA-V/J junction. This suggests that some positions of the axolotl CDR3 alpha chain loop are positively selected during T-cell differentiation, particularly around residue 93 that could be selected for its ability to makes contacts with major histocompatibility complex-associated antigenic peptides, as in mammals. The axolotl Calpha domain had the typical structure of mammalian and avian Calpha domains, including the charged residues in the TM segment that are thought to interact with other proteins in the membrane, as well as most of the residues forming the conserved antigen receptor transmembrane motif. PMID:9002443

  14. CD4+CD25+Treg细胞与支气管哮喘%CD4+ CD25+ Treg cells and bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    鞠云飞; 孙立锋; 胡华

    2011-01-01

    The main function of CD4+ CD25+ Treg cells are immunological anergy and inhibition,which is essential to the maintenance of immunological tolerance in the host.CD4+ CD25+ Treg cells produce inhibitory cytokines (TGF-β and IL-10),express membrane molecules (CTLA-4,GITR,etc) and Foxp3.There are abnormal in function and quantity of CD4+ CD25+ Treg cells of peripheral blood from asthmatic patients,which maybe one of the pathogenesis of asthma.Glucocorticoids can inhibit the airway inflamation of asthma by impacting CD4+ CD25+ Treg cells.%CD4+ CD25+ Treg细胞的主要作用表现为免疫无能性和免疫抑制性,是外周免疫耐受形成机制的主要组成部分.其主要作用机制为分泌抑制性细胞因子(IL-10和TGF-β)、表达细胞表面分子(CTLA-4、GITR等)及Foxp3等.支气管哮喘患者外周血CD4+ CD25+ Treg功能及数量存在异常,这可能是支气管哮喘发病机制之一.糖皮质激素可以通过影响CD4+ CD25+ Treg的状态起到抑制支气管哮喘气道炎症的作用.

  15. Study of the Alpha-Decay Chain for7753 194Rn with Relativistic Mean-Field Theory

    Institute of Scientific and Technical Information of China (English)

    SHENG Zong-Qiang; GUO Jian-You

    2008-01-01

    The structures of the nuclei on the alpha-decay chain of 194Rn are investigated in the deformed relativistic mean-field theory with the effective interaction TMA. We put an emphasis on the ground state properties of 194Rn. The calculated alpha-decay energies and lifetimes are both very close to the experimental data for 186pb and 190po. For 194 Rn, the deviations are a little large on both the alpha-decay energy and the lifetime. We also calculate the alpha-decay energies for the isotopes 192~208Rn. The tendency for the change of the alpha-decay energies with neutron number is correctly reproduced in the relativistic mean-field theory (RMF). In general, the RMF theory can give a good description of the alpha decay chain of 194Rn.

  16. A shortened beta-hexosaminidase alpha-chain in an Italian patient with infantile Tay-Sachs disease.

    OpenAIRE

    Zokaeem, G; Bayleran, J; Kaplan, P; Hechtman, P; Neufeld, E F

    1987-01-01

    Fibroblasts derived from a beta-hexosaminidase A (HexA)-deficient infant with clinically classic Tay-Sachs disease synthesized a precursor alpha-chain that was smaller than its normal counterpart. Fibroblasts from the infant's parents, who were consanguinous, produced both normal and mutant alpha-chains. The size difference, estimated to be 2-3 kilodaltons on the basis of sodium dodecyl sulfate-polyacrylamide-gel electrophoresis, persisted after removal of oligosaccharides with endo-H and is ...

  17. TRAIL对肿瘤侵润CD4+CD25+Treg的调节作用%Regulation of TRAIL on tumor infiltrating CD4+CD25+Treg

    Institute of Scientific and Technical Information of China (English)

    袁海芹; 刁智娟; 周剑锁; 刘彦信; 史娟; 郑德先

    2011-01-01

    0bjective:To investigate the regulation of TRAIL on tumor infiltrating CD 4+ CD25 +Treg cells.Methods:The inpact of TRAL on CCL22 secretion of tumor cells was detected by ELISA .Recam binant soluble TRAL was adminsttated into subcutaneous solid 4T1 tumor and tumor volum e was measured .Tumor infiltrating lym phocytes w ere isolated and assayed by flow cytam etry to evaluate the change of CD4+ CD25+ Treg cells in umor.Results:rsTRAIL increased CCL22 secretion into supematant of tumor cell 4Tl and B16 cells.TRAIL treat ment did notinhibit the s .C.4T1 tumor growth ,but turmor infiltrating CD 4+ CD25+ Treg increased obviously .Conclusion :Augmention in CCL22 secretion of 4T1 cancer cells might recruit Tregs,therefore, leading to turmor infiltrating CD 4+CD 25+Treg increase .This study provides novel data tor the physiological function research of TRAIL and cancer therapy application .%目的:探讨TRAIL对肿瘤侵润CD4+CD25+Treg细胞的调节作用.方法:ELISA检测TRAIL对肿瘤细胞分泌CCL22的影响;建立对TRAIL耐受的4T1肿瘤细胞皮下实体瘤模型,瘤内给予重组TRAIL蛋白,检测肿瘤体积的变化;分离肿瘤侵润的淋巴细胞,采用流式细胞术检测瘤内CD4+CD25+Treg细胞的变化.结果:TRAIL引起肿瘤细胞4T1和B16培养上清中CCL22水平增加;TRAIL治疗组与对照组相比,对TRAIL耐受的4T1移植瘤体积没有明显变化,但TRAIL治疗组的肿瘤侵润CD4+CD25+Treg细胞显著增加.结论:TRAIL引起肿瘤细胞分泌CCL22,可因此诱导CD4+CD25+Treg细胞趋化至肿瘤部位导致肿瘤侵润的CD4+CD25+Treg比例增加,为TRAIL的生理功能和在肿瘤治疗中的应用提供了新的资料.

  18. CD25 shedding by human natural occurring CD4+CD25+ regulatory T cells does not inhibit the action of IL-2

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Lauritsen, Jens Peter Holst

    2009-01-01

    Regulatory T (Treg) cells are important for the maintenance of peripheral tolerance and inhibition of pathogenic T-cell responses. Therefore, they are important for the limitation of chronic inflammation but can also be deleterious by e.g. limiting antitumour immune responses. Natural occurring...... Tregs are known to inhibit CD4+ T cell in a contact-dependent manner, but at the same time, various suppressive factors are secreted. We, here, demonstrate that human naturally occurring CD4+CD25+ Tregs are able to shed large amounts of soluble CD25 upon activation. Secretion of sCD25 could add to the...... inhibitory effect of Tregs as such secretion in other settings has been proposed to act as a sink for local IL-2. However, we here demonstrate that supernatant from human Tregs containing high concentration of sCD25 does not inhibit proliferation of CD4+CD25(-) T cells or inhibit the action of IL-2 in an in...

  19. CD4+CD25+Treg细胞与支气管哮喘%CD4+CD25+Treg cells and bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    鞠云飞; 孙立锋; 胡华

    2011-01-01

    CD4+CD25+Treg细胞的主要作用表现为免疫无能性和免疫抑制性,是外周免疫耐受形成机制的主要组成部分.其主要作用机制为分泌抑制性细胞因子(IL-10和TGF-β)、表达细胞表面分子(CTLA-4、GITR等)及Foxp3等.支气管哮喘患者外周血CD4+CD25+Treg功能及数量存在异常,这可能是支气管哮喘发病机制之一.糖皮质激素可以通过影响CD4+CD25+Treg的状态起到抑制支气管哮喘气道炎症的作用.

  20. Involvement of CD4+CD25+ regulatory T cells in the pathogenesis of polycythaemia vera

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wen-bo; LI Ying; LIU Xin; ZHANG Ling-yan; WANG Xin

    2008-01-01

    Background Regulatory T cells (Treg) have been shown to play an important role in the regulation of hematopoietic activity. However, there is no information about the effect of Treg cells in the pathogenesis of polycythaemia vera (PV).Methods In this study, we investigated the percentage and function of Treg cells in the peripheral blood of 21 PV patients and 25 healthy donors. Treg cells were identified and characterized as CD4+CD25+FOXP3+ by flow cytometry.The suppressive activity of CD4+CD25+ Treg cells was assessed by the proliferation and cytokine secretion of the co-cultured CD4+CD25- fractions.Results The results showed that the percentage of Treg cells in the peripheral blood of PV patients significantly increased compared to healthy controls ((10.93±4.02)% vs (5.86±1.99)%, P <0.05). Moreover, the mRNA and protein expression of FOXP3 was higher in CD4+CD25+ Treg cells. Coordinately, when co-cultured with the activated CD4+CD25-cells, the CD4+CD25+ Treg cells showed enhanced suppressive function in PV. Yet, the underlying mechanism for the increased frequency and function of CD4+CD25+ Treg cells is still to be clarified.Conclusion Treg cells expansion might account for the abnormal T cell immunity in PV patients and thus contribute to the pathogenesis of PV.

  1. CD4~+Foxp3~+ regulatory T cells converted by rapamycin from peripheral CD4~+ CD25~-naive T cells display more potent regulatory ability in vitro

    Institute of Scientific and Technical Information of China (English)

    CHEN Jian-fei; GAO Jie; ZHANG Dong; WANG Zi-han; ZHU Ji-ye

    2010-01-01

    Background Rapamycin (RAPA) is a relatively new immunosuppressant drug that functions as a serine/threonine kinase inhibitor to prevent rejection in organ transplantation. RAPA blocks activation of T-effector (Teff) cells by inhibiting the response to interleukin-2. Recently, RAPA was also shown to selectively expand the T-regulator (Treg) cell population. To date, no studies have examined the mechanism by which RAPA converts Teff cells to Treg cells. Methods Peripheral CD4~+CD25~- naive T cells were cultivated with RAPA and B cells as antigen-presenting cells (APCs) in vitro. CD4~+CD25~- T cells were harvested after 6 days and analyzed for expression of forkhead box protein 3 (Foxp3) using flow cytometry. CD4~+CD25~+CD127~- subsets as the converted Tregs were isolated from the mixed lymphocyte reactions (MLR) with CD127 negative selection, followed by CD4 and CD25 positive selection using microbeads and magnetic separation column (MSC). Moreover, mRNA was extracted from converted Tregs and C57BL/6 naive CD4~+CD25~+ T cells and Foxp3 levels were examined by quantitative real-time polymerase chain reaction (rt-PCR). A total of 1×10~5 carboxyfluorescein succinimidyl ester (CFSE)-labeled naive CD4~+CD25~- T cells/well from C57BL/6 mice were cocultured with DBA/2 or C3H maturation of dendritic cells (mDCs) (0.25×10~5/well) in 96-well round-bottom plates for 6 days. Then 1×10~5 or 0.25×10~5 converted Treg cells were added to every well as regulatory cells. Cells were harvested after 6 days of culture and analyzed for proliferation of CFSE-labeled naive CD4~+CD25~- T cells using flow cytometry. Data were analyzed using CellQuest software.Results We found that RAPA can convert peripheral CD4~+CD25~- naive T Cells to CD4~+Foxp3~+ Treg cells using B cells as APCs, and this subtype of Treg can potently suppress Teff proliferation and maintain antigenic specificity. Conclusion Our findings provide evidence that RAPA induces Treg cell conversion from Teff cells and

  2. Central muscarinic cholinergic activation alters interaction between splenic dendritic cell and CD4+CD25- T cells in experimental colitis.

    Directory of Open Access Journals (Sweden)

    Peris Munyaka

    Full Text Available BACKGROUND: The cholinergic anti-inflammatory pathway (CAP is based on vagus nerve (VN activity that regulates macrophage and dendritic cell responses in the spleen through alpha-7 nicotinic acetylcholine receptor (a7nAChR signaling. Inflammatory bowel disease (IBD patients present dysautonomia with decreased vagus nerve activity, dendritic cell and T cell over-activation. The aim of this study was to investigate whether central activation of the CAP alters the function of dendritic cells (DCs and sequential CD4+/CD25-T cell activation in the context of experimental colitis. METHODS: The dinitrobenzene sulfonic acid model of experimental colitis in C57BL/6 mice was used. Central, intracerebroventricular infusion of the M1 muscarinic acetylcholine receptor agonist McN-A-343 was used to activate CAP and vagus nerve and/or splenic nerve transection were performed. In addition, the role of α7nAChR signaling and the NF-kB pathway was studied. Serum amyloid protein (SAP-A, colonic tissue cytokines, IL-12p70 and IL-23 in isolated splenic DCs, and cytokines levels in DC-CD4+CD25-T cell co-culture were determined. RESULTS: McN-A-343 treatment reduced colonic inflammation associated with decreased pro-inflammatory Th1/Th17 colonic and splenic cytokine secretion. Splenic DCs cytokine release was modulated through α7nAChR and the NF-kB signaling pathways. Cholinergic activation resulted in decreased CD4+CD25-T cell priming. The anti-inflammatory efficacy of central cholinergic activation was abolished in mice with vagotomy or splenic neurectomy. CONCLUSIONS: Suppression of splenic immune cell activation and altered interaction between DCs and T cells are important aspects of the beneficial effect of brain activation of the CAP in experimental colitis. These findings may lead to improved therapeutic strategies in the treatment of IBD.

  3. Murine laminin alpha3A and alpha3B isoform chains are generated by usage of two promoters and alternative splicing.

    Science.gov (United States)

    Ferrigno, O; Virolle, T; Galliano, M F; Chauvin, N; Ortonne, J P; Meneguzzi, G; Aberdam, D

    1997-08-15

    We already identified two distinct laminin alpha3A and alpha3B chain isoforms which differ in their amino-terminal ends and display different tissue-specific expression patterns. In this study we have investigated whether these two different isoforms are products of the same laminin alpha3 (lama3) gene and transcribed from one or two separate promoters. Genomic clones were isolated that encompass the sequences upstream to the 5' ends of both the alpha3A and the alpha3B cDNAs. Sequence analysis of the region upstream to the alpha3A open reading frame revealed the presence of a TATA box and potential binding sites for responsive elements. By primer extension analysis, the transcription start site of the alpha3B mRNA isoform was defined. The sequences upstream to the alpha3B mRNA transcription start site do not contain a TATA box near the transcription initiation sites, but AP-1, AP-2, and Sp1 consensus binding site sequences were identified. The genomic regions located immediately upstream of the alpha3A and alpha3B transcription start sites were shown to possess promoter activities in transfection experiments. In the promoter regions, response elements for the acute phase reactant signal and NF-interleukin 6 were found, and their possible relevance in the context of inflammation and wound healing is discussed. Our results demonstrate that the lama3 gene produces the two polypeptides by alternative splicing and contains two promoters, which regulate the production of the two isoforms alpha3A and alpha3B. PMID:9252362

  4. HB KURDISTAN [ALPHA-47(CE5)ASP-]TYR], A NEW ALPHA-CHAIN VARIANT IN COMBINATION WITH BETA-THALASSEMIA

    NARCIS (Netherlands)

    GIORDANO, PC; HARTEVELD, CL; STRENG, H; Oosterwijk, Jan; HEISTER, JGAM; AMONS, R; BERNINI, LF

    1994-01-01

    We have characterized the structural abnormality of a new alpha chain mutant found in a Kurdish; family. The clinical and hematological investigation of eight individuals have shown that the a variant is associated with a beta degrees-thalassemia mutation (nonsense codon 39). The tryptic peptide map

  5. The generation and antigen-specificity of CD4+CD25+ regulatory T cells.

    Science.gov (United States)

    Taams, Leonie S; Curnow, S John; Vukmanovic-Stejic, M; Akbar, Arne N

    2006-09-01

    CD4+CD25+ regulatory T cells are essential components of the immune system. They help to maintain immune tolerance by exerting suppressive effects on cells of the adaptive and innate immune system. In the last few years there has been an abundance of papers addressing the suppressive effects of CD4+CD25+ regulatory T cells and their putative role in various experimental disease models and human diseases. Despite the enormous amounts of data on these cells a number of controversial issues still exists. CD4+CD25+ regulatory T cells were originally described as thymus-derived anergic/suppressive T cells. Recent papers however indicate that these cells might also be generated in the periphery. Due to the thymic development of CD4+CD25+ regulatory T cells it was thought that these cells were specific for self-antigens. Indeed it was shown that CD4+CD25+ regulatory T cells could be positively selected upon high affinity interaction with self-antigens. However, evidence is accumulating that these cells might also interact with non-self antigens. Finally, in the literature there is conflicting evidence regarding the role of soluble factors versus cell-contact in the mechanism of suppression. The aim of this review is to summarize the evidence supporting these opposing viewpoints and to combine them into a general model for the origin, function and antigen-specificity of CD4+CD25+ regulatory T cells. PMID:16918478

  6. Predictions on the alpha decay chains of superheavy nuclei with Z =121 within the range 290 $\\leq$ A $\\leq$ 339

    CERN Document Server

    Santhosh, K P

    2016-01-01

    A systematic study on the alpha decay half lives of various isotopes of superheavy element \\textit{Z} = 121 within the range 290 $\\leq$ A $\\leq$ 339 is presented for the first time using Coulomb and proximity potential model for deformed nuclei (CPPMDN). The calculated $\\alpha$ decay half lives of the isotopes within our formalism match well with the values computed using Viola-Seaborg systematic, Universal curve of Poenaru et al., and the analytical formula of Royer. In our study by comparing the $\\alpha$ decay half lives with the spontaneous fission half lives, we have predicted $2\\alpha$ chain from $^{309, 311, 312}$121, $3\\alpha$ chain from $^{310}$121 and $1\\alpha$ chain from $^{313, 314}$121. Clearly our study shows that the isotopes of superheavy element \\textit{Z} = 121 within the mass range 309 $\\leq$ A $\\leq$ 314 will survive fission and can be synthesized and detected in the laboratory via alpha decay. We hope that our predictions will provide a new guide to future experiments.

  7. $^{110,116}$Cd($\\alpha,\\alpha$)$^{110,116}$Cd elastic scattering and systematic investigation of elastic $\\alpha$ scattering cross sections along the $Z$ = 48 isotopic and $N$ = 62 isotonic chains

    CERN Document Server

    Kiss, G G; Fülöp, Zs; Gyürky, Gy; Elekes, Z; Farkas, J; Somorjai, E; Yalcin, C; Galaviz, D; Güray, R T; Özkan, N; Görres, J

    2013-01-01

    The elastic scattering cross sections for the reactions $^{110,116}$Cd($\\alpha,\\alpha$)$^{110,116}$Cd at energies above and below the Coulomb barrier are presented to provide a sensitive test for the alpha-nucleus optical potential parameter sets. Additional constraints for the optical potential are taken from the analysis of elastic scattering excitation functions at backward angles which are available in literature. Moreover, the variation of the elastic alpha scattering cross sections along the $Z = 48$ isotopic and $N = 62$ isotonic chain is investigated by the study of the ratios of the of $^{106,110,116}$Cd($\\alpha,\\alpha$)$^{106,110,116}$Cd scattering cross sections at E$_{c.m.} \\approx$ 15.6 and 18.8 MeV and the ratio of the $^{110}$Cd($\\alpha,\\alpha$)$^{110}$Cd and $^{112}$Sn($\\alpha,\\alpha$)$^{112}$Sn reaction cross sections at E$_{c.m.} \\approx$ 18.8 MeV, respectively. These ratios are sensitive probes for the alpha-nucleus optical potential parameterizations. The potentials under study are a basic...

  8. CD+4CD+25调节性T细胞与肿瘤的相关性研究%CD+4 CD+25 regulatory T cells and lung cancer

    Institute of Scientific and Technical Information of China (English)

    翟晋芳; 韩福才

    2009-01-01

    通过了解CD+4 CD+25调节性T细胞(CD+4 CD+25Treg)表面分子的特性和CD+4 CD+25Treg在外周血和组织中的表达,认识CD+4 CD+25 Treg在肿瘤免疫凋节中的作用,探索其作用的分子机制.%To know CD+4 CD+25 regulatory T cells' s function in tumor immunological regulation and to search for its functionary molecule mechanism by reviewing researches associated with the characteristics of CD+4 CD+25 regulatory T cells surface molecules and the expression of CD+4 CD+25 regulatory T cells in the peripheral blood and tissues.

  9. Murine branched chain alpha-ketoacid dehydrogenase kinase; cDNA cloning, tissue distribution, and temporal expression during embryonic development.

    Science.gov (United States)

    Doering, C B; Coursey, C; Spangler, W; Danner, D J

    1998-06-01

    These studies were designed to demonstrate the structural and functional similarity of murine branched chain alpha-ketoacid dehydrogenase and its regulation by the complex-specific kinase. Nucleotide sequence and deduced amino acid sequence for the kinase cDNA demonstrate a highly conserved coding sequence between mouse and human. Tissue-specific expression in adult mice parallels that reported in other mammals. Kinase expression in female liver is influenced by circadian rhythm. Of special interest is the fluctuating expression of this kinase during embryonic development against the continuing increase in the catalytic subunits of this mitochondrial complex during development. The need for regulation of the branched chain alpha-ketoacid dehydrogenase complex by kinase expression during embryogenesis is not understood. However, the similarity of murine branched chain alpha-ketoacid dehydrogenase and its kinase to the human enzyme supports the use of this animal as a model for the human system. PMID:9611264

  10. Effects of estrogen on CD4+CD25+ regulatory T cell in peripheral blood during pregnancy

    Institute of Scientific and Technical Information of China (English)

    Yuan-Huan Xiong; Zhen Yuan; Li He

    2013-01-01

    Objective:To investigate the effects of estrogen (E2) level on regulatory T cells (Treg) in peripheral blood during pregnancy. Methods:A total of 30 healthy non-pregnant women were selected as control group, 90 pregnant women of early, middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group, middle pregnancy group and late pregnancy group;the proportions of CD4+CD25+Treg and CD4+CD25+CD127-Treg among CD4+T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method. Results: E2 level was coincident with the change of Tregs number during pregnancy. The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy, then decreased significantly after parturition, and the level at 1 month after parturition down to the level in non-pregnancy group (P>0.05);the level of E2 in pregnancy groups were significantly higher than those in non-pregnancy group (P0.05);the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group (P0.05). There was correlation between Tregs number with estrogen level during pregnancy. The proportion of CD4+CD25+ Treg and CD4+CD25+CD127- Treg were positively correlated with estrogen level. Conclusions:High proportion of CD4+CD25+Treg and CD4+CD25+CD127-Treg is closely related to the high level of E2 during pregnancy. It suggested that high level of estrogen may induce an increase of CD4+CD25+Treg in peripheral blood, and then influence the immune function of pregnant women. The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.

  11. Natural CD4~+CD25~+ regulatory T cells express α7-nicotinic acetylcholine receptor subunits%小鼠天然CD4~+CD25~+调节性T细胞表达α7烟碱型乙酰胆碱受体

    Institute of Scientific and Technical Information of China (English)

    王大伟; 周荣斌; 姚咏明

    2010-01-01

    Objective To investigate whether CD4~+ CD25~+ regulatory T cells (Treg) from C57BL/6J mice express alpha7 nicotinic acetylcholine receptor (α7nAChR). Methods CD4~+ CD25~+ regulatory T cells were isolated from mouse splenocytes with a CD4~+ CD25~+ regulatory T Cell isolation kit (Mihenyi Bio-tee). The purity of isolated Tregs was analyzed by flow eytometry. Expressions of α7nAChR in mouse CD4~+ CD25~+ Tregs were examined by immunofluorescence staining, Western blotting, and reverse transeription-PCR, respectively. Results It was revealed by flow cytometry that Tregs could bind alpha-bungarotoxin (α-BGT)-F/TC, a specific α7 nAChR antagonist. Moreover, a positive binding to α-Bgt was also observed on the cell surface of Treg, as viewed by fluorescent confoeal microscopy. In addition, a clear band of a7nAChR with a molecular mass of approximately 55 kD was found from Tregs by Western blotting analysis, and α7nAChR mRNA was expressed with the expected size of 199 bp from Tregs by reverse transcription-PCR. Conclusion Natural CD4~+ CD25~+ Tregs from mice express α7nAChR.%目的 探讨C57BL/6J小鼠的天然CD4~+CD25~+调节性T细胞(CD4~+CD25~+Treg)是否存在α7烟碱型乙酰胆碱受体(a7nAchR).方法 使用小鼠调节性T细胞试剂盒分离小鼠脾脏CD4~+CD25~+Treg,流式细胞术鉴定CD4~+CD25~+Treg的纯度.分别采用免疫荧光染色、共聚焦湿微镜、Western印迹和逆转录聚合酶链反应检测Treg表面α7nAchR蛋白/基因表达.结果 α-银环蛇毒素-FITC染色、流式检测显示Treg细胞表面结合α-银环蛇毒素-FITC;共聚焦显微镜成像观察到Treg细胞表面结合大量α-银环蛇毒素;Western印迹检测证实Treg细胞样本中检测到了清楚的α7nAchR条带,分子量大小约为55 kD;RT-PCR分析发现Treg细胞样本中检测到了199 bp大小的特异性α7nAchR目的 基因条带.结论小鼠天然CD4~+CD25~+Treg细胞表达α7nAChR.

  12. Promiscuous presentation and recognition of nucleosomal autoepitopes in lupus: role of autoimmune T cell receptor alpha chain.

    Science.gov (United States)

    Shi, Y; Kaliyaperumal, A; Lu, L; Southwood, S; Sette, A; Michaels, M A; Datta, S K

    1998-02-01

    T cells specific for nucleosomal autoepitopes are selectively expanded in lupus mice and these Th cells drive autoimmune B cells to produce pathogenic antinuclear antibodies. We transfected the TCR-alpha and -beta chain genes of a representative, pathogenic autoantibody-inducing Th clone specific for the nucleosomal core histone peptide H471-94 into TCR-negative recipient cells. Although the autoimmune TCRs were originally derived from SNF1 (I-Ad/q) mice, the transfectants could recognize the nucleosomal autoepitope presented by APC-bearing I-A molecules of all haplotypes tested, as well as human DR molecules. Competition assays indicated that the autoepitopes bound to the MHC class II groove. Most remarkably, MHC-unrestricted recognition of the nucleosomal peptide epitope was conferred by the lupus TCR-alpha chain even when it paired with a TCR-beta chain of irrelevant specificity. Several other disease-relevant Th clones and splenic T cells of lupus mice had similar properties. The TCR-alpha chains of these murine lupus Th clones shared related motifs and charged residues in their CDRs, and similar motifs were apparent even in TCR-alpha chains of human lupus Th clones. The lupus TCR-alpha chains probably contact the nucleosomal peptide complexed with MHC with relatively high affinity/avidity to sustain TCR signaling, because CD4 coreceptor was not required for promiscuous recognition. Indeed, pathogenic autoantibody-inducing, CD4-negative, TCR-alphabeta+ Th cells are expanded in systemic lupus erythematosus. These results have implications regarding thymic selection and peripheral expansion of nucleosome-specific T cells in lupus. They also suggest that universally tolerogenic epitopes could be designed for therapy of lupus patients with diverse HLA alleles. We propose to designate nucleosomes and other antigens bearing universal epitopes "Pantigens" (for promiscuous antigens).

  13. Diminished CD4+/CD25+ T cell and increased IFN-gamma levels occur in dogs vaccinated with Leishmune in an endemic area for visceral leishmaniasis.

    Science.gov (United States)

    de Lima, Valéria Marçal Felix; Ikeda, Fabiana Augusta; Rossi, Cláudio N; Feitosa, Mary Marcondes; Vasconcelos, Rosemeride Oliveira; Nunes, Caris Maroni; Goto, Hiro

    2010-06-15

    The Leishmune vaccine has been used in endemic areas to prevent canine visceral leishmaniasis in Brazil, but cytokine production induced by vaccination has rarely been investigated in dogs. This study aimed to evaluate the immune response of dogs vaccinated with Leishmune FML vaccine (Fort Dodge) against total antigen of Leishmania (Leishmania) chagasi (TAg) and FML. Twenty healthy dogs from Araçatuba, São Paulo, Brazil, an endemic leishmaniasis area, received three consecutive subcutaneous injection of Leishmune vaccine at 21-day intervals. PBMC were isolated before and 10 days after completing vaccination and lymphoproliferative response and antibody production against FML or total promastigote antigen were tested. Cytokines IFN-gamma, IL-4 and TNF-alpha were measured in culture supernatant and CD4+/CD25+ and CD8+/CD25+ T cell presence was determined. Analysis of the data indicated that the vaccine conferred humoral responses (100%) against both antigens and cellular immunity to FML (85%) and total antigen (80%), the supernatant of cultured cells stimulated with TAg and FML showed an increase in IFN-gamma (P<0.05), and the vaccine reduced CD4+/CD25+ T cell presence compared to that observed before vaccination. These responses may constitute part of the immune mechanism induced by Leishmune.

  14. Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro✩

    OpenAIRE

    Secor, Eric R.; Singh, Anurag; Guernsey, Linda A.; McNamara, Jeff T.; Zhan, Lijun; Maulik, Nilanjana; Thrall, Roger S.

    2009-01-01

    Bromelain (Br), an extract from pineapple stem with cysteine protease activity, exerts anti-inflammatory effects in a number of inflammatory models. We have previously shown that Br treatment decreased activated CD4+ T cells and has a therapeutic role in an ovalbumin-induced murine model of allergic airway disease. The current study was designed to determine the effect of Br on CD4+ T cell activation, specifically the expression of CD25 in vitro. CD25 is up regulated upon T cell activation, f...

  15. CD4+CD25+调节性T细胞对哮喘大鼠免疫功能影响%Effect of CD4+CD25+Regulatory T Cells on the Immunologic Function in Rats with Asthma

    Institute of Scientific and Technical Information of China (English)

    薛克营; 金卫国; 王成国; 程立; 杨中卫; 王正艳

    2009-01-01

    目的:观察CD4+CD25+调节性T细胞(CD4+CD25+Treg)对CD4+CD25-T细胞增殖和Th1/Th2细胞因子分泌的影响,探讨其在哮喘气道炎症中的作用机制.方法:将哮喘大鼠CD4+CD25-T细胞分别与卵白蛋白(OVA)免疫耐受大鼠CD4+Cd25+Treg细胞和哮喘大鼠CD4+CD25+Treg细胞联合培养,3H胸腺嘧啶核苷(3H-TdR)掺入法测量细胞增殖情况,ELISA检测细胞IL-4、IL-5和IFN-γ含量.结果:OVA耐受大鼠CD4+CD25+Treg细胞能抑制CD4+CD25-T细胞增殖和Th2细胞因子分泌(P<0.05);哮喘大鼠CD4+CD25+Treg细胞可明显抑制IFN-γ的分泌(P<0.05).结论:OVA免疫耐受大鼠CD4+CD25+Treg细胞可能通过抑制哮喘大鼠CD4+CD25-T细胞增殖和影响Th1/Th2平衡发挥作用,哮喘大鼠CD4+CD25+Treg细胞存在功能异常,可能与哮喘的发病有关.

  16. Cloning of the LamA3 gene encoding the alpha 3 chain of the adhesive ligand epiligrin. Expression in wound repair.

    Science.gov (United States)

    Ryan, M C; Tizard, R; VanDevanter, D R; Carter, W G

    1994-09-01

    We have isolated cDNA clones encoding the entire 170-kDa chain of epiligrin (alpha 3Ep) and a genomic clone encoding the alpha 3Ep gene (LamA3). Analysis of multiple cDNA clones revealed two distinct transcripts (alpha 3EpA and alpha 3EpB). Sequencing of the alpha 3EpA transcript indicated sequence and structural homology to laminin alpha 1 and alpha 2 chains that extend from domain IIIa through the carboxyl-terminal G domain. The alpha 3EpB transcript encodes a larger amino-terminal domain and contains additional epidermal growth factor repeats and sequences corresponding to domain IV of alpha 1 laminin. Fluorescence in situ hybridization indicated that the LamA3 gene is located on chromosome 18q11.2, a locus distinct from the LamA1 gene (18p11.3). The G domain of the epiligrin alpha 3 chain contains five subdomains that are individually related to the G subdomains reported for Drosophila and vertebrate laminin alpha chains. Sequence divergence within the G domain of alpha 3 epiligrin suggests that it is functionally distinct from laminin, consistent with our previous report showing that epiligrin interacts with different integrin adhesion receptors. Analysis of RNA from human foreskin keratinocytes (HFKs) identified multiple epiligrin transcripts that were down-regulated by viral transformation and differentiation. In contrast, epiligrin expression was up-regulated in wound sites of human skin. PMID:8077230

  17. Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3

    OpenAIRE

    Chen, Wanjun; Jin, Wenwen; Hardegen, Neil; Lei, Ke-Jian; Li, Li; Marinos, Nancy; McGrady, George; Wahl, Sharon M.

    2003-01-01

    CD4+CD25+ regulatory T cells (Treg) are instrumental in the maintenance of immunological tolerance. One critical question is whether Treg can only be generated in the thymus or can differentiate from peripheral CD4+CD25− naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4+CD25− T cells into anergic/suppressor cells that are CD25+, CD45RB−/low and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transformin...

  18. Expression of regulatory CD4+CD25+ Treg,CD4+CD25higTreg cells and Foxp3 mRNA in wheezing infants and its clinical significance%CD4+CD25+、CD4+CD25hig调节性T细胞和Foxp3mRNA在婴幼儿喘息中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    彭力; 钟礼立; 黄寒; 厉娟; 梁沫; 李云

    2012-01-01

    Objective To evaluate the changes of CD4+ CD25+ Treg,CD4 +CD25hig Treg and Foxp3 mRNA in peripheral blood from wheezing infantsMethods Fifty-one wheezing infants and twenty healthy volunteers were included in this study. The proportion of CD4 + CD25 + Treg and CD4 + CD25hig Treg population in total T cells was evaluated by flow cytometric analysis. The expression of Foxp3 mRNA was tested by flow cytometry. Total serum IgE of wheezy infants was detected by enzyme immunoassay. Results Compared with those of healthy control, the frequency of CD4 + CD25 + Treg and CD4 + CD25hig Treg in the peripheral blood from wheezing infants showed a significant increase (6. 31 + 2. 96) % / (3.52 + 1.46) % ,P<0. 01 ,P<0. 01, respectively).The expression of CD4 + CD25+ Treg,CD4 + CD25hig Treg and Foxp3 mRNA in peripheral blood from wheezing infants with atopy burden was lower than those from non-wheezing infants(P<0. 05). The correlation analysis showed that CD4 + CD25hig Treg (r= -0. 75 , P<0.01) and Foxp3 mRNA(r= -0. 61,P<0. 01) had significantly positive relation with total serum IgE,while CD4+CD25 + Treg had significantly negative relation with total serum IgE(r=0. 36,P<0. 05). Conclusion CD4+CD25+ Treg, CD4+CD25hig Treg and Foxp3 mRNA play an important role in activation of wheezing infants.%目的 探讨婴幼儿喘息CD4+CD25+、CD4+CD25hig调节性T细胞(Treg)和叉头/翼状螺旋转录因子(Foxp3)mRNA的表达及意义.方法 采用流式细胞术检测51例首次喘息婴幼儿外周血CD4+CD25+Treg和CD4+CD25higTreg的比例,RT-PCR检测Foxp3 mRNA的表达量,酶联免疫吸附法(ELASA)检测总IgE水平,并与正常婴幼儿对照.结果 喘息婴幼儿外周血CD4+CD25+Treg、CD4+CD25higTreg占CD4+T细胞的百分比分别为(6.31+2.96)%和(3.52+1.46)%,均明显低于健康对照组(P<0.01);特应征喘息组CD4+CD25+Treg、CD4+CD25higTreg及Foxp3 mRNA表达均低于非特应征喘息组(P<0.05).喘息患儿CD4+CD25higTreg百分率及Foxp3 mRNA表达与

  19. Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

    Directory of Open Access Journals (Sweden)

    Marcilene Rezende Silva

    2013-01-01

    Full Text Available OBJECTIVE: To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. METHODS: βS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. RESULTS: The following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5 Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13 Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2 Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5 Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. CONCLUSION: Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

  20. CD8{sup +}CD25{sup +} T cells reduce atherosclerosis in apoE(−/−) mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jianchang; Dimayuga, Paul C.; Zhao, Xiaoning; Yano, Juliana; Lio, Wai Man; Trinidad, Portia; Honjo, Tomoyuki; Cercek, Bojan; Shah, Prediman K.; Chyu, Kuang-Yuh, E-mail: Chyuk@cshs.org

    2014-01-17

    Highlights: •The role of a sub-population of CD8{sup +} T cells with suppressor functions was investigated in atherosclerosis. •CD8{sup +}CD25{sup +} T cells from adult apoE(−/−) mice had phenotype characteristics of T suppressor cells. •These CD8{sup +}CD25{sup +} T cells reduced CD4{sup +} T cell proliferation and CD8{sup +} cytotoxic activity in vitro. •Adoptive transfer of CD8{sup +}CD25{sup +} T cells significantly reduced atherosclerosis. •CD8{sup +}CD25{sup +} T cells have a suppressive function in atherosclerosis. -- Abstract: Background: It is increasingly evident that CD8{sup +} T cells are involved in atherosclerosis but the specific subtypes have yet to be defined. CD8{sup +}CD25{sup +} T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis were investigated in this study. Methods and results: CD8{sup +}CD25{sup +} T cells were observed in atherosclerotic plaques of apoE(−/−) mice fed hypercholesterolemic diet. Characterization by flow cytometric analysis and functional evaluation using a CFSE-based proliferation assays revealed a suppressive phenotype and function of splenic CD8{sup +}CD25{sup +} T cells from apoE(−/−) mice. Depletion of CD8{sup +}CD25{sup +} from total CD8{sup +} T cells rendered higher cytolytic activity of the remaining CD8{sup +}CD25{sup −} T cells. Adoptive transfer of CD8{sup +}CD25{sup +} T cells into apoE(−/−) mice suppressed the proliferation of splenic CD4{sup +} T cells and significantly reduced atherosclerosis in recipient mice. Conclusions: Our study has identified an athero-protective role for CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis.

  1. Use of CD25 as an immunohistochemical marker for acquired ocular toxoplasmosis

    Directory of Open Access Journals (Sweden)

    Cristina Miyamoto

    2010-10-01

    Full Text Available PURPOSE: Toxoplasmosis is the most common cause of posterior infectious uveitis worldwide. It is often impossible to determine its congenital or acquired nature. Interleukin-2 (IL-2 in peripheral blood has been described as a possible marker for acquired toxoplasmosis. The purpose of this study is to evaluate the histopathological characteristics of ocular toxoplasmosis cases using CD25 as a marker for the expression of interleukin-2. METHODS: Ten formalin-fixed, paraffin-embedded enucleated globes from ten immunocompetent patients with clinical diagnosis of toxoplasmosis were evaluated. Four patients had the acquired form of ocular toxoplasmosis (positive IgM while six were IgM negative and IgG positive for toxoplasmosis. Histopathological slides were reviewed for the extension of the retinal necrosis, number of toxo cysts, the granulomatous inflammatory reaction, the presence of T and B cells within the choroid and the IL-2 expression. Immunohistochemistry using monoclonal antibodies was performed to observe the expression of CD4, CD8, CD20, CD25, and CD68. RESULTS: The histopathological evaluation disclosed no differences between acquired and the other ocular toxoplasmosis cases regarding the characteristics studied. However, CD25 showed a higher expression of IL-2 on the 4 acquired cases of ocular toxoplasmosis compared to the remainders. CONCLUSIONS: To the best of our knowledge, this is the first report showing that the use of CD25 as a marker for interleukin-2 could differentiate acquired ocular toxoplasmosis.

  2. IL-35, an anti-inflammatory cytokine which expands CD4+CD25+ Treg Cells.

    Science.gov (United States)

    Castellani, Maria Luisa; Anogeianaki, A; Felaco, P; Toniato, E; De Lutiis, M A; Shaik, B; Fulcheri, M; Vecchiet, J; Tetè, S; Salini, V; Theoharides, T C; Caraffa, A; Antinolfi, P; Frydas, I; Conti, P; Cuccurullo, C; Ciampoli, C; Cerulli, G; Kempuraj, D

    2010-01-01

    Interleukin 12 (IL 12) p35/p40 is a heterodimeric cytokine which plays a critical role in inflammation, immunity and tissue proliferation, and also plays a relevant function in T helper (Th) cell polarization and Th1 T-cell differentiation. IL-12 family members, IL-12p70, IL-23, IL-27 and IL-35, play an important role in influencing helper T-cell differentiation. EBV-induced gene 3 can be associated with the p35 subunit of IL-12 to form the EBI3/p35 heterodimer, also called IL-35. It has been shown that IL-35 has biological activity and able to expand CD4+CD25+ Treg cells, suppress the proliferation of CD4+CD25- effector cells and inhibit Th17 cell polarization. IL-35 has been shown to be constitutively expressed by regulatory T (Treg) cells CD4(+)CD25(+)Foxp3(+) and suggested to contribute to their suppressive activity. IL-35 is a crucial mediator which provokes CD4+CD25+ T cell proliferation and IL-10 generation, another well-known anti-inflammatory cytokine, along with TGFbeta cytokine. These studies suggest that IL-35, together with other successfully discovered cytokine inhibitors, represents a new potential therapeutic cytokine for chronic inflammation, autoimmunity and other immunological disorders.

  3. CD4+CD25+ regulatory T cells: I. Phenotype and physiology

    DEFF Research Database (Denmark)

    Holm, Thomas Lindebo; Nielsen, Janne; Claesson, Mogens H

    2004-01-01

    it has become increasingly clear that regulatory CD4+CD25+ T cells (Treg cells) play an important role in the maintenance of immunological self-tolerance, and that this cell subset exerts its function by suppressing the proliferation or function of autoreactive T cells. Based on human and murine...

  4. Electroacupuncture Attenuates Ovalbumin-Induced Allergic Asthma via Modulating CD4+CD25+ Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Youngjoo Kwon

    2012-01-01

    Full Text Available A mouse pulmonary hypersensitivity experimental model that mimics human asthma was developed, and electroacupuncture (EA treatment was shown to reduce allergic inflammatory processes. In addition, we also assessed whether the beneficial effects of EA on allergic asthma could be correlated with CD4+CD25+Foxp3+ regulatory T cells (Treg. Cellular profiles and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly decreased in the EA-treated groups when compared to the OVA and anti-CD25 Ab-injected (Treg depletion groups. Furthermore, total BAL cells were reduced in the EA groups when compared to other groups. Interestingly, the population of CD4+CD25+Foxp3+Tregs in pneumonocytes increased in EA-treated group when compared to OVA and Treg depletion groups. These results imply that EA stimulation at ST 36 may affect CD4+CD25+Foxp3+ Treg in an OVA-induced experimental model and may enhance Treg function by suppressing other T cells and limiting the immune response.

  5. CD4+CD25+ regulatory T cells: II. Origin, disease models and clinical aspects

    DEFF Research Database (Denmark)

    Nielsen, Janne; Holm, Thomas Lindebo; Claesson, Mogens H

    2004-01-01

    Autoimmune diseases afflict approximately 5% of the population and reflect a failure in the immune system to discriminate between self and non-self resulting in the breakdown of self-tolerance. Regulatory CD4+CD25+ T cells (Treg cells) have been shown to play an important role in the maintenance ...

  6. Reactivity of naive CD4+CD25- T cells against gut microflora in healthy mice

    DEFF Research Database (Denmark)

    Gad, Monika; Lundsgaard, Dorthe; Kjellev, Stine;

    2006-01-01

    We have previously shown that conventional as well as germ-free CD4+ T cells depleted of CD25+ cells from the gut-associated lymphoid tissue and the periphery proliferate specifically in response to enterobacterial antigen exposure whereas unfractionated CD4+ T cells are not reactive under these ...

  7. Efficient induction of CD25- iTreg by co-immunization requires strongly antigenic epitopes for T cells

    Directory of Open Access Journals (Sweden)

    Li Jinyao

    2011-05-01

    Full Text Available Abstract Background We previously showed that co-immunization with a protein antigen and a DNA vaccine coding for the same antigen induces CD40low IL-10high tolerogenic DCs, which in turn stimulates the expansion of antigen-specific CD4+CD25-Foxp3+ regulatory T cells (CD25- iTreg. However, it was unclear how to choose the antigen sequence to maximize tolerogenic antigen presentation and, consequently, CD25- iTreg induction. Results In the present study, we demonstrated the requirement of highly antigenic epitopes for CD25- iTreg induction. Firstly, we showed that the induction of CD25- iTreg by tolerogenic DC can be blocked by anti-MHC-II antibody. Next, both the number and the suppressive activity of CD25- iTreg correlated positively with the overt antigenicity of an epitope to activate T cells. Finally, in a mouse model of dermatitis, highly antigenic epitopes derived from a flea allergen not only induced more CD25- iTreg, but also more effectively prevented allergenic reaction to the allergen than did weakly antigenic epitopes. Conclusions Our data thus indicate that efficient induction of CD25- iTreg requires highly antigenic peptide epitopes. This finding suggests that highly antigenic epitopes should be used for efficient induction of CD25- iTreg for clinical applications such as flea allergic dermatitis.

  8. CD4(+)CD25 (+)CD127 (low/-) T cells: a more specific Treg population in human peripheral blood.

    Science.gov (United States)

    Yu, Ning; Li, Xiaomei; Song, Weiya; Li, Dongmei; Yu, Daliang; Zeng, Xiaofeng; Li, Mengtao; Leng, Xiaomei; Li, Xiangpei

    2012-12-01

    The quantitative identification and enrichment of viable regulatory T cells (Treg) requires reliable surface markers that are selectively expressed on Treg. Foxp3 is the accepted marker of nTreg, but it cannot be used to isolate cells for functional studies. In this study, we compared four staining profiles of Treg, including CD4(+)CD25(high) T cells, CD4(+)CD39(+) T cells, CD4(+)CD73(+) T cells, and CD4(+)CD25(+)CD127(low/-) T cells. We found that CD4(+)CD25(+)CD127(low/-) T cells expressed the highest level of Foxp3 and had the strongest correlation with CD4(+)CD25(+)Foxp3(+) T cells, the accepted identifying characteristics for "real" nTreg cells. Moreover, functional data showed that CD4(+)CD25(+)CD127(low/-) T cells could effectively suppress the proliferation of CD4(+)CD25(-) T cells, suggesting that compared with the other three populations, CD4(+)CD25(+)CD127(low/-) T cells best fit the definition of naturally occurring regulatory T cells in human peripheral blood. Finally, we showed that CD4(+)CD25(+)CD127(low/-) can be used to quantitate Treg cells in individuals with systemic lupus erythematosus supporting the use of CD4(+)CD25(+)CD127(low/-) to identify human Treg cells. PMID:22752562

  9. Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

    International Nuclear Information System (INIS)

    Highlights: → Curcumin inhibits CD4+ T-lymphocyte proliferation. → Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4+ T-lymphocytes. → Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. → IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4+ T-lymphocytes, as well as interleukin-2 (IL-2) and CD25chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca2+ release to inhibit IκB phosphorylation, which is required for nuclear translocation of the transcription factor NFκB. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4+CD25+ regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

  10. Allo-PBSCT患者CD4+CD25+调节性T细胞的体外研究%Study on post-allogeneic peripheral blood stem cell transplantation patients'CD4 + CD25 + regulatory T cells in vitro

    Institute of Scientific and Technical Information of China (English)

    翟海龙; 赖永榕

    2011-01-01

    Objective To investigate the proliferation reaction of CD4+ CD25+ Tregs in the stimulating of costimulato-ry signal, lymphocyte reactions mixed with CD4+ CD25- T cells of CD4+ CD25+ Tregs, and cytokine secretion state of the two cells in allogeneic peripheral blood stem cell transplantation ( Allo-PBSCT) patients. Methods CD4+ CD2S+ Tregs and CD4+ CD25- T cells from peripheral blood obtained from 36 patients who had undergone Allogeneic peripheral blood stem cell transplantation (Allo-PBSCT), 7 healthy volunteers as control, were isolated with magnetic cells sorting separation. Then CD4+ CD25+ Tregs and CD4+ CD25+ Tregs + CD4+ CD25- T cells were cultered for 72 hours, stimulated by an-ti-CD3-mAbs and anti-CD28-mAbs. After that the cultures added with CCK-8 solution were incubated for 1 hour. Then OD450 were detected by ELISA. IL-10, TGF-β and IFN-γ from the two above cell cultures were detected by ELISA method. Results OD450 values of CD4+ CD25+ Tregs were both extremely lower than that of CD4+ CD25- T cells and CD4+ CD25+ Tregs + CD4+ CD25- T cells( P < 0.01). IL-10, TGF-p and IFN-γ secreted by CD4 + CD25+ Tregs in vitro from patients with and without GVHD were signigicantly lower than that of CD4+ CD25- T cells( P < 0.01 ). The 3 cytokines secreted by CD4+ CD25- Tregs + CD4+ CD25- T cells group were also signigicantly lower than that of CD4+ CD25- T cells( P <0.05 ). The cytokines secretory of Allo-PBSCT group was similar with that of control group. Conclusions If the suppressive function of CD4+ CD25+ Tregs are utilized, incidence of GVHD post- Allo-PBSCT may decrease.%目的 探讨异基因外周血干细胞移植(Allo-PBSCT)患者外周血CD4+ CD25+调节性T细胞(Tregs)在协同刺激信号作用下的增殖反应、与CD4+ CD25 -T细胞混合淋巴细胞反应及上述两种培养细胞的细胞因子分泌情况.方法 对36例Allo-PBSCT患者离体CD4+ CD25+ Tregs在抗CD3-mAbs和抗CD28-mAbs的刺激下行CD4+CD25 +Tregs培养和CD4+ CD25+ Tregs、CD4

  11. Separation and Amplification of CD4 + CD25 + Regulatory T Cells from Sensitized Mice%致敏小鼠CD4+CD25+调节性T细胞磁珠分选及体外扩增

    Institute of Scientific and Technical Information of China (English)

    潘莉; 翁文骏; 许吕宏; 魏菁; 方建培

    2012-01-01

    The aim of this study was to separate and amplify CD4 + CD25 + Treg cells from splenocytes of sensitized nrice. The percentage of CD4 + CD25 + Treg cells was detected by flow cytometty in sensitized and normal control mice. CD4 + T, CD4 + CD25 + Treg and CD4' CD25" T cells were isolated from mouse splenocytes by MACS. CD4 + CD25+ Treg cells were expanded in vitro cultures in addition of CD3/CD28 MACSiBead and IL-2. The activity of cells was detected with 0.4% trypan blue staining. The purity of cells after sorting, the main surface marker and the level of Foxp3 were detected by flow cytometry. The results showed that CD4 + CD25 + Treg cell proportion was higher in sensitized mice than normal control mice ( P 0.05). It is concluded that the sorting of CD4 + CD25 + Treg cells is isolated successfully by MACS without affecting the vitality of target cells. The amplification of CD4 + CD25 + Treg cells is successral in vitro. Expression of surface markers and Faxp3 gene does not obviously change after amplification, so that to establish a practical method to recover and enlarge the amount of CD4 + CD25 + Treg cells in good condition.%本研究探讨致敏小鼠CD4+ CD25+调节性T细胞的分选及体外扩增.流式细胞术检测致敏小鼠及正常小鼠体内CD4+ CD25+ Treg细胞水平,免疫磁珠分选方法从小鼠脾细胞中分选出CD4+T细胞、CD4+ CD25+ Treg细胞和CD4+ CD25-T细胞,负载抗CD3/CD28单克隆抗体MACSiBead联合IL-2共同刺激CD4+ CD25+ Treg细胞进行体外扩增培养,用0.4%台盼蓝染色并计数检测细胞的活性,流式细胞术检测分选后细胞纯度、主要表面标记及Foxp3基因的表达.结果表明:致敏小鼠体内CD4+ CD25+ Treg水平较正常小鼠升高(P<0.05).分选出CD4+ CD25+Treg细胞纯度平均达到87%,细胞活性大于97%,高表达Foxp3基因.体外扩增2周后细胞数扩增倍数能够达到42倍,CD4+ CD25+ Treg细胞所占比例为85.32%,Foxp3表达由(76.92±1.72)%稍下降至(75

  12. Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis.

    Science.gov (United States)

    Hahn, Hejin P; Hornick, Jason L

    2007-11-01

    Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This

  13. Structural Origins of Nitroxide Side Chain Dynamics on Membrane Protein [alpha]-Helical Sites

    Energy Technology Data Exchange (ETDEWEB)

    Kroncke, Brett M.; Horanyi, Peter S.; Columbus, Linda (UV)

    2010-12-07

    Understanding the structure and dynamics of membrane proteins in their native, hydrophobic environment is important to understanding how these proteins function. EPR spectroscopy in combination with site-directed spin labeling (SDSL) can measure dynamics and structure of membrane proteins in their native lipid environment; however, until now the dynamics measured have been qualitative due to limited knowledge of the nitroxide spin label's intramolecular motion in the hydrophobic environment. Although several studies have elucidated the structural origins of EPR line shapes of water-soluble proteins, EPR spectra of nitroxide spin-labeled proteins in detergents or lipids have characteristic differences from their water-soluble counterparts, suggesting significant differences in the underlying molecular motion of the spin label between the two environments. To elucidate these differences, membrane-exposed {alpha}-helical sites of the leucine transporter, LeuT, from Aquifex aeolicus, were investigated using X-ray crystallography, mutational analysis, nitroxide side chain derivatives, and spectral simulations in order to obtain a motional model of the nitroxide. For each crystal structure, the nitroxide ring of a disulfide-linked spin label side chain (R1) is resolved and makes contacts with hydrophobic residues on the protein surface. The spin label at site I204 on LeuT makes a nontraditional hydrogen bond with the ortho-hydrogen on its nearest neighbor F208, whereas the spin label at site F177 makes multiple van der Waals contacts with a hydrophobic pocket formed with an adjacent helix. These results coupled with the spectral effect of mutating the i {+-} 3, 4 residues suggest that the spin label has a greater affinity for its local protein environment in the low dielectric than on a water-soluble protein surface. The simulations of the EPR spectra presented here suggest the spin label oscillates about the terminal bond nearest the ring while maintaining weak

  14. Effect of alpha thalassaemia trait and enhanced gamma chain production on disease severity in beta thalassaemia major and intermedia.

    OpenAIRE

    Gringras, P; Wonke, B; Old, J.; Fitches, A; Valler, D; Kuan, A M; Hoffbrand, V

    1994-01-01

    One hundred and twenty patients with homozygous beta thalassaemia were selected to determine the clinical effects of certain genetic factors which may modify disease severity. Genetic analysis defined specific beta thalassaemia mutations, the alpha thalassaemia genotype, and the presence of an XmnI restriction enzyme site, associated with increased fetal haemoglobin (HbF) production under certain conditions. Genotypic data with globin chain synthesis were related to the age when regular trans...

  15. Evidence of balanced diversity at the chicken interleukin 4 receptor alpha chain locus

    Directory of Open Access Journals (Sweden)

    Podisi Baitsi

    2009-06-01

    Full Text Available Abstract Background The comparative analysis of genome sequences emerging for several avian species with the fully sequenced chicken genome enables the genome-wide investigation of selective processes in functionally important chicken genes. In particular, because of pathogenic challenges it is expected that genes involved in the chicken immune system are subject to particularly strong adaptive pressure. Signatures of selection detected by inter-species comparison may then be investigated at the population level in global chicken populations to highlight potentially relevant functional polymorphisms. Results Comparative evolutionary analysis of chicken (Gallus gallus and zebra finch (Taeniopygia guttata genes identified interleukin 4 receptor alpha-chain (IL-4Rα, a key cytokine receptor as a candidate with a significant excess of substitutions at nonsynonymous sites, suggestive of adaptive evolution. Resequencing and detailed population genetic analysis of this gene in diverse village chickens from Asia and Africa, commercial broilers, and in outgroup species red jungle fowl (JF, grey JF, Ceylon JF, green JF, grey francolin and bamboo partridge, suggested elevated and balanced diversity across all populations at this gene, acting to preserve different high-frequency alleles at two nonsynonymous sites. Conclusion Haplotype networks indicate that red JF is the primary contributor of diversity at chicken IL-4Rα: the signature of variation observed here may be due to the effects of domestication, admixture and introgression, which produce high diversity. However, this gene is a key cytokine-binding receptor in the immune system, so balancing selection related to the host response to pathogens cannot be excluded.

  16. Tissue-specific expression of the human laminin alpha5-chain, and mapping of the gene to human chromosome 20q13.2-13.3 and to distal mouse chromosome 2 near the locus for the ragged (Ra) mutation

    DEFF Research Database (Denmark)

    Durkin, M E; Loechel, F; Mattei, M G;

    1997-01-01

    To investigate the function of the laminin alpha5-chain, previously identified in mice, cDNA clones encoding the 953-amino-acid carboxy terminal G-domain of the human laminin alpha5-chain were characterized. Northern blot analysis showed that the laminin alpha5-chain is expressed in human placent...

  17. A polymorphic variant in the human electron transfer flavoprotein alpha-chain (alpha-T171) displays decreased thermal stability and is overrepresented in very-long-chain acyl-CoA dehydrogenase-deficient patients with mild childhood presentation

    DEFF Research Database (Denmark)

    Bross, P; Pedersen, P; Nyholm, M;

    1999-01-01

    , whereas the two variants of the beta-M/T154 polymorphism did not differ. We wished to test the hypothesis that these polymorphisms might constitute susceptibility factors and therefore determined their allele and genotype frequencies in (i) control individuals, (ii) medium-chain acyl-CoA dehydrogenase......-deficient patients homozygous for the K304E mutation (MCAD E304), (iii) a group of patients with elevated urinary excretion of ethylmalonic acid (EMA) possibly due to decreased short-chain acyl-CoA dehydrogenase activity, and (iv) in patients with proven deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD......). No significant overrepresentations or underrepresentations were found in the first two patient groups, suggesting that the polymorphisms studied are not significant susceptibility factors in either the MCAD E304 or the EMA patient group. However, in the VLCAD deficient patients the alpha-T171 variant (decreased...

  18. Expression of Ets-1 and FOXP3 mRNA in CD4(+)CD25 (+) T regulatory cells from patients with systemic lupus erythematosus.

    Science.gov (United States)

    Xiang, Nan; Li, Xiang-Pei; Li, Xiao-Mei; Wang, Guo-Sheng; Tao, Jin-Hui; Pan, Hai-Feng; Fang, Xuan; Ma, Qian; Yu, Ning

    2014-11-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complex genetic predisposing factors involved. Ets-1 transcription factor plays an important role in the suppressive activity of CD4(+)CD25(+) Treg cells and stable expression of FOXP3. To find its potential role in the pathogenesis of SLE, we investigate the mRNA expression of Ets-1 and FOXP3 mRNA in CD4(+)CD25(+) Treg cells from patients with SLE. Real-time transcription-polymerase chain reaction analysis was used to determine the expression of Ets-1 and FOXP3 mRNA in CD4(+)CD25(+) Treg cells from 36 patients with SLE and 18 sex-and-age-matched healthy controls. The Ets-1 mRNA expression level was decreased in patients with SLE [0.225 (0.135, 0.337)] than healthy controls [0.528 (0.303, 0.681)] (P Ets-1 and FOXP3 expression was also found in new-onset SLE subgroup when compared with healthy controls (P Ets-1 and FOXP3 mRNA was not significantly different in hyperactive and lower active SLE group when compared with inactive SLE group, respectively (P > 0.05). There were no significant differences between SLE with lupus nephritis (LN) and SLE without LN either (P > 0.05). Associations of Ets-1 and FOXP3 mRNA expression levels with major clinical and laboratory parameters of SLE patients were also analyzed. However, no significant association was found. Significant positive correlation was found between Ets-1 and FOXP3 mRNA expression in CD4(+)CD25(+) Treg cells from SLE patients (r = 0.698, P Ets-1 mRNA were decreased in SLE patients and Ets-1 expression was positively correlated with the expression of FOXP3. It indicated that Ets-1 may play an important role in the stable expression of FOXP3 in CD4(+)CD25(+) Treg cells.

  19. Electroacupuncture Attenuates Ovalbumin-Induced Allergic Asthma via Modulating CD4+CD25+ Regulatory T Cells

    OpenAIRE

    Youngjoo Kwon; Sung-Hwa Sohn; Gihyun Lee; Youngeun Kim; Hyejung Lee; Minkyu Shin; Hyunsu Bae

    2012-01-01

    A mouse pulmonary hypersensitivity experimental model that mimics human asthma was developed, and electroacupuncture (EA) treatment was shown to reduce allergic inflammatory processes. In addition, we also assessed whether the beneficial effects of EA on allergic asthma could be correlated with CD4+CD25+Foxp3+ regulatory T cells (Treg). Cellular profiles and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly decreased in ...

  20. Glucocorticoid induced TNFR-related protein (GITR as marker of human regulatory T cells: expansion of the GITR+CD25- cell subset in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    E. Bartoloni Bocci

    2011-06-01

    Full Text Available Objectives: Regulatory T cells (TREG represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/ inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR is a well known marker of murine TREG cells, but little is known in humans. The aim of this study was to investigate the characteristics of TREG cells in systemic lupus erythematosus (SLE and the potential role of GITR as marker of human TREG. Methods: Nineteen SLE patients and 15 sex- and age-matched normal controls (NC were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies and real time polymerase-chain reaction (PCR using TaqMan probes. Results: The CD25highGITRhigh subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05. On the opposite, the CD25-GITRhigh cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01. Interestingly, FoxP3 at mRNA level was expressed in both CD25- GITRhigh and CD25highGITRhigh cells, suggesting that both cell subsets have regulatory activity. Conclusions: CD4+CD25-GITRhigh cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset.

  1. CD4(+)CD25(hi)Foxp3(+) Cells Exacerbate Bleomycin-Induced Pulmonary Fibrosis.

    Science.gov (United States)

    Birjandi, Shirin Z; Palchevskiy, Vyacheslav; Xue, Ying Ying; Nunez, Stefanie; Kern, Rita; Weigt, S Sam; Lynch, Joseph P; Chatila, Talal A; Belperio, John A

    2016-08-01

    Idiopathic pulmonary fibrosis is a fatal lung disease with a median survival of 2 to 5 years. A decade of studies has downplayed inflammation contributing to its pathogenesis. However, these studies preceded the discovery of regulatory T cells (Tregs) and all of their functions. On the basis of human studies demonstrating Tregs can decrease graft-versus-host disease and vasculitides, there is consideration of their use to treat idiopathic pulmonary fibrosis. We hypothesized that Treg therapy would attenuate the fibroplasia involved in a preclinical murine model of pulmonary fibrosis. IL-2 complex was used in vivo to expand CD4(+)CD25(hi)Foxp3(+) cells in the lung during intratracheal bleomycin challenge; however, this unexpectedly led to an increase in lung fibrosis. More important, this increase in fibrosis was a lymphocyte-dependent process. We corroborated these results using a CD4(+)CD25(hi)Foxp3(+) cellular-based therapy. Mechanistically, we demonstrated that CD4(+)CD25(hi)Foxp3(+) cells undergo alterations during bleomycin challenge and the IL-2 complex had no effect on profibrotic (eg, transforming growth factor-β) or type 17 immune response cytokines; however, there was a marked down-regulation of the type 1 and augmentation of the type 2 immune response cytokines from the lungs. Collectively, our animal studies show that a specific lung injury can induce Treg alterations, which can augment pulmonary fibrosis. PMID:27317904

  2. Substitution of a conserved cysteine-996 in a cysteine-rich motif of the laminin {alpha}2-chain in congenital muscular dystrophy with partial deficiency of the protein

    Energy Technology Data Exchange (ETDEWEB)

    Nissinen, M.; Xu Zhang; Tryggvason, K. [Univ. of Oulu (Finland)

    1996-06-01

    Congenital muscular dystrophies (CMDs) are autosomal recessive muscle disorders of early onset. Approximately half of CMD patients present laminin {alpha}2-chain (merosin) deficiency in muscle biopsies, and the disease locus has been mapped to the region of the LAMA2 gene (6q22-23) in several families. Recently, two nonsense mutations in the laminin {alpha}2-chain gene were identified in CMD patients exhibiting complete deficiency of the laminin {alpha}2-chain in muscle biopsies. However, a subset of CMD patients with linkage to LAMA2 show only partial absence of the laminin {alpha}2-chain around muscle fibers, by immunocytochemical analysis. In the present study we have identified a homozygous missense mutation in the {alpha}2-chain gene of a consanguineous Turkish family with partial laminin {alpha}2-chain deficiency. The T{r_arrow}C transition at position 3035 in the cDNA sequence results in a Cys996{r_arrow}Arg substitution. The mutation that affects one of the conserved cysteine-rich repeats in the short arm of the laminin {alpha}2-chain should result in normal synthesis of the chain and in formation and secretion of a heterotrimeric laminin molecule. Muscular dysfunction is possibly caused either by abnormal disulfide cross-links and folding of the laminin repeat, leading to the disturbance of an as yet unknown binding function of the laminin {alpha}2-chain and to shorter half-life of the muscle-specific laminin-2 and laminin-4 isoforms, or by increased proteolytic sensitivity, leading to truncation of the short arm. 42 refs., 7 figs.

  3. Association of the IL2RA/CD25 Gene With Juvenile Idiopathic Arthritis

    Science.gov (United States)

    Hinks, Anne; Ke, Xiayi; Barton, Anne; Eyre, Steve; Bowes, John; Worthington, Jane; Thompson, Susan D; Langefeld, Carl D; Glass, David N; Thomson, Wendy

    2009-01-01

    Objective IL2RA/CD25, the gene for interleukin-2 receptor α, is emerging as a general susceptibility gene for autoimmune diseases because of its role in the development and function of regulatory T cells and the association of single-nucleotide polymorphisms (SNPs) within this gene with type 1 diabetes mellitus (DM), Graves' disease, rheumatoid arthritis (RA), and multiple sclerosis (MS). The aim of this study was to determine whether SNPs within the IL2RA/CD25 gene are associated with juvenile idiopathic arthritis (JIA). Methods Three SNPs within the IL2RA/CD25 gene, that previously showed evidence of an association with either RA, MS, or type 1 DM, were selected for genotyping in UK JIA cases (n = 654) and controls (n = 3,849). Data for 1 SNP (rs2104286) were also available from North American JIA cases (n = 747) and controls (n = 1,161). Association analyses were performed using Plink software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results SNP rs2104286 within the IL2RA/CD25 gene was significantly associated with UK JIA cases (OR for the allele 0.76 [95% CI 0.66–0.88], P for trend = 0.0002). A second SNP (rs41295061) also showed modest evidence for association with JIA (OR 0.80 [95% CI 0.63–1.0], P = 0.05). Association with rs2104286 was convincingly replicated in the North American JIA cohort (OR 0.84 [95% CI 0.65–0.99], P for trend = 0.05). Meta-analysis of the 2 cohorts yielded highly significant evidence of association with JIA (OR 0.76 [95% CI 0.62–0.88], P = 4.9 × 10−5). Conclusion These results provide strong evidence that the IL2RA/CD25 gene represents a JIA susceptibility locus. Further investigation of the gene using both genetic and functional approaches is now required. PMID:19116909

  4. CD4+CD25+调节性T细胞在支气管哮喘中的研究进展%The researches on CD4+CD25+ Treg in bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    李营营; 冯学斌

    2007-01-01

    CD4+CD25+调节性T细胞(CD4+CD25+Treg)是一种表型和功能特异的T细胞亚群,它在抑制自身免疫性疾病的发生,诱导机体免疫耐受机制中发挥着重要作用.研究CD4+CD25+Treg在支气管哮喘中的功能机制,对阐明哮喘的发病机制及探索疾病免疫治疗方面有重要意义.

  5. Synthesis of beta-hexosaminidase in cell-free translation and in intact fibroblasts: an insoluble precursor alpha chain in a rare form of Tay-Sachs disease.

    OpenAIRE

    Proia, R L; Neufeld, E F

    1982-01-01

    RNA was isolated from human term placenta or cultured fibroblasts and translated in a rabbit reticulocyte system in the presence of [35S]methionine; the translation products were immunoprecipitated with antisera made against beta-hexosaminidase or its isolated alpha and beta chains and analyzed by polyacrylamide gel electrophoresis. The largest translated alpha and beta chain polypeptides had Mrs of 65,000 and 59,000, respectively. These are approximately equal to 2,000 greater than the Mrs o...

  6. Analysis of human T-cell lymphotropic virus in CD25+ anaplastic large cell lymphoma in children.

    Science.gov (United States)

    Gualco, Gabriela; Chioato, Lucimara; Weiss, Lawrence M; Harrington, William J; Bacchi, Carlos E

    2009-07-01

    Anaplastic large cell lymphoma (ALCL) is recognized as 2 distinct diseases: anaplastic lymphoma kinase (ALK)+ ALCL and ALK- ALCL. ALK+ ALCL occurs in younger patients and has a better prognosis. Human T-cell lymphotropic virus (HTLV-1) is linked to the development of adult T-cell leukemia/lymphoma (ATLL), which frequently expresses CD25. CD25 is significantly expressed in childhood ALCL. In Brazil, HTLV-1 infection is endemic, and vertical transmission is responsible for spread to children. Of HTLV-1 carriers, 90% or more remain asymptomatic. Some cases of adult HTLV-1-related lymphomas have characteristics of ALCL but are considered CD30+ ATLL subtypes. No similar cases have been described in children. We analyzed 33 cases of pediatric ALCL, CD25+ and CD25-, for proviral HTLV-1 DNA. All cases corresponded to the common histologic ALCL type and were CD30+ in virtually all neoplastic cells. ALK expression was observed in 31 (94%) of 33 cases; CD25 was positive in 27 (82%), including 1 ALK- ALCL case. There was a strong positive correlation between ALK and CD25 expression. None of the cases showed proviral HTLV-1 DNA. ALCL in children has no relationship with HTLV-1; the frequent CD25 expression must be explained by a mechanism different from that in ATLL.

  7. Structure effects in the region of superheavy elements via the $\\alpha$-decay chain of $^{293}$118

    CERN Document Server

    Gupta, Raj K; Kumar, Rajesh; Balasubramaniam, M; Scheid, W; 10.1088/0954-3899/28/11/310

    2011-01-01

    The $\\alpha$-decay chain of $^{293}$118, first proposed in the Berkeley cold fusion experiment $^{208}$Pb($^{86}$Kr,1n) and now retracted, is calculated by using the preformed cluster model (PCM) of one of us (RKG). Also, the possible branchings of $\\alpha$-particles to heavier cluster decays of all the parents in this chain are calculated for the first time. The calculated Q-values, penetrabilities and preformation factors for $\\alpha$-decays suggest that the $^{285}$114 nucleus with Z=114, N=171 is a magic nucleus, either due to the magicity of Z=114, or of N=172 or of both. The N=172 is proposed to be a magic number in certain relativistic mean-field calculations, but with Z=120. The calculated cluster decays point to new interesting possibilities of $^{14}$C decay of the $^{281}$112 parent, giving rise to a (reasonably) deformed Z=106, N=161, $^{267}$106 daughter (N=162 being now established as the deformed magic shell) or to a doubly magic $^{48}$Ca cluster emitted from any of the parent nucleus in the $...

  8. cDNA sequence coding for the alpha'-chain of the third complement component in the African lungfish.

    Science.gov (United States)

    Sato, A; Sültmann, H; Mayer, W E; Figueroa, F; Tichy, H; Klein, J

    1999-04-01

    cDNA clones coding for almost the entire C3 alpha-chain of the African lungfish (Protopterus aethiopicus), a representative of the Sarcopterygii (lobe-finned fishes), were sequenced and characterized. From the sequence it is deduced that the lungfish C3 molecule is probably a disulphide-bonded alpha:beta dimer similar to that of the C3 components of other jawed vertebrates. The deduced sequence contains conserved sites presumably recognized by proteolytic enzymes (e.g. factor I) involved in the activation and inactivation of the component. It also contains the conserved thioester region and the putative site for binding properdin. However, the site for the interaction with complement receptor 2 and factor H are poorly conserved. Either complement receptor 2 and factor H are not present in the lungfish or they bind to different residues at the same or a different site than mammalian complement receptor 2 and factor H. The C3 alpha-chain sequences faithfully reflect the phylogenetic relationships among vertebrate classes and can therefore be used to help to resolve the long-standing controversy concerning the origin of the tetrapods. PMID:10219761

  9. CD4+CD25+调节性T细胞及其分子标记物与支气管哮喘%CD4+CD25+regulatory T cell and its molecular marker with bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    马祥; 毛辉; 梁宗安

    2009-01-01

    CD4+CD25+regulatory T cells are a kind of lymphocytes characterized by immune inhibition and immune inability,FOXP3 is a specific molecular marker of CD4+CD25+regulatory T cells,and critical for the generation,peripheral expression and function of CD4+CD25+regulatory T cells.In recent years,a series of studies showed that CD4+CD25+regulatory T cells interfere with the development and progression of bronchial asthma,the intervention of regulatory T cell and its relative genes may offer a novel therapeutic strategy for bronchial asthma.%CD4+CD25+调节性T细胞是一类以免疫抑制和免疫无能为特征的淋巴细胞群,FOXP3是CD4+CD25+调节性T细胞一个特征性的分子标志物,并且对CD4+CD25+调节性T细胞的发育、外周表达和功能维持有着关键性的作用.近年来,多项研究显示CD4+CD25+调节性T细胞参与并影响了支气管哮喘的发生、发展过程,对调节性T细胞或其相关基因的干预也许会成为支气管哮喘治疗的新方向.

  10. Expression and significance of CD4+ CD25+ Foxp3+ T cells in the acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation%骨髓或外周血中CD4+CD25+Foxp3+调节性T淋巴细胞与aGVHD的关系

    Institute of Scientific and Technical Information of China (English)

    王晓娟; 车传珍; 周昱男; 刘仲萍; 黄士昂

    2009-01-01

    目的 研究患者异基因造血干细胞移植(allo-HSCT)前后骨髓或外周血单个核细胞中CD4+CD25+Foxp3+调节性T淋巴细胞(以下简称CD4+CD25+Foxp3+T细胞)的比率、Foxp3 mRNA和Foxp3蛋白的表达与急性移植物抗宿主病(aGVHD)的关系.方法 选择37例行HIA相合异基因造血干细胞移植(allo-HSCT))的患者作为研究对象.采用流式细胞术检测患者allo-HSCT前7天(-7 d)、移植当天(0 d)、移植后30天(+30d)、+60 d和+90 d时骨髓或外周血单个核细胞中CD4+CD25+Foxp3+T细胞所占的比率;定量聚合酶链反应(PCR)检测Foxp3 mRNA相对表达量;蛋白印迹(Western blot)法检测Foxp3的蛋白表达水平.结果 37例患者存移植后100 d内发生aGVHD 13例(aGVHD组),未发生aGVHD 24例(无aGVHD组).CD4+CD25+Foxp3+T细胞的比率在0 d时最低,与-7、+30、+60、+90d时比较.差异均有统计学意义(P<0.01);与aGVHD组比较,无aGVHD组患者的CD4+CD25+Foxp3+T细胞的比率明显升高,差异有统计学意义(P<0.01).aGVHD组患者移植后Foxp3的表达水平逐渐升高,但明显低于无aGVHD组,尤其在+60和+90 d时的差异有统计学意义(P<0.01).Western blot法检测结果 表明,aGVHD组受者的Foxp3蛋白表达也明显低于无aGVHD组.结论 CD4+CD25+Foxp3+T细胞对防止发生aGVHD具有重要作用,监测患者骨髓或外周血中CD4+CD25+Foxp3+T细胞的比率可以预测aGVHD的发生.%Objective To investigate the expression and significance of CD4+ CD25+ Foxp3+ T Cells, Foxp3 mRNA and Foxp3 protein in the acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Thirty-seven donor grafts and their respective clinical characteristics were evaluated. Flow cytometric analysis was performed to assess the percentage of CD4+ CD25+ Foxp3+ T cells in the recipients before, and 0, 30, 60, and 90 days after allo-HSCT. The relative expression of Foxp3 mRNA was detected by real time reverse transcription-polymerase chain

  11. Mutation in the alpha 5(IV) collagen chain in juvenile-onset Alport syndrome without hearing loss or ocular lesions

    DEFF Research Database (Denmark)

    Zhou, J; Hertz, Jens Michael; Tryggvason, K

    1992-01-01

    A single base mutation was identified in the type IV collagen alpha 5 chain gene (COL4A5) of a Danish kindred with Alport syndrome. The 27-year-old male proband developed hematuria in childhood and terminal renal failure at the age of 25 years. He has no hearing loss or ocular lesions. Electron.......9-kb fragments present in control DNA but the presence of a 2.2-kb variant fragment, indicating the loss of an MspI restriction site in the 3' end of the gene. The mother had all three fragments, indicating heterozygosity. PCR amplification of exon 14 (counted from the 3' end) and subsequent denaturing...

  12. 56 Increased Frequency of CD4+ CD25+ FOXP3- in Allergic Conjunctivitis Patients

    OpenAIRE

    Galicia-Carreón, Jorge; Alonso-Sánchez, Miguel E.; Robles-Contreras, Atzin; Hong, Enrique; Chávez, Raul; Jiménez-Martínez, Maria C.

    2012-01-01

    Background Allergic conjunctivitis (AC) is one of the most common eye disorders in clinical practice. It has been shown that AC is a disorder mediated by Th2 lymphocytes producing IL-4 and IL-5, where the eye damage is caused by a type I hypersensitivity. It has been suggested in asthma and rhinitis that T regulatory cells (Tregs) CD4+ CD25+ FOXP3+ have been involved in control allergic status, favoring an optimal microenvironment with immunosuppressive cytokines (IL-10, TGF-β). However is un...

  13. Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and saposin B but increased expression of an inter-alpha-trypsin inhibitor heavy chain 4 fragment.

    Science.gov (United States)

    Jayapalan, Jaime J; Ng, Keng L; Shuib, Adawiyah S; Razack, Azad H A; Hashim, Onn H

    2013-06-01

    The present study was aimed at the identification of proteins that are differentially expressed in the urine of patients with prostate cancer (PCa), those with benign prostatic hyperplasia (BPH) and age-matched healthy male control subjects. Using a combination of 2DE and MS/MS, significantly lower expression of urinary saposin B and two different fragments of inter-alpha-trypsin inhibitor light chain (ITIL) was demonstrated in the PCa patients compared to the controls. However, only one of the ITIL fragments was significantly different between the PCa and BPH patients. When image analysis was performed on urinary proteins that were transferred onto NC membranes and detected using a lectin that binds to O-glycans, a truncated fragment of inter-alpha-trypsin inhibitor heavy chain 4 was the sole protein found to be significantly enhanced in the PCa patients compared to the controls. Together, these urinary peptide fragments might be useful complementary biomarkers to indicate PCa as well as to distinguish it from BPH, although further epidemiological evidence on the specificity and sensitivity of the protein candidates is required. PMID:23417432

  14. Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and saposin B but increased expression of an inter-alpha-trypsin inhibitor heavy chain 4 fragment.

    Science.gov (United States)

    Jayapalan, Jaime J; Ng, Keng L; Shuib, Adawiyah S; Razack, Azad H A; Hashim, Onn H

    2013-06-01

    The present study was aimed at the identification of proteins that are differentially expressed in the urine of patients with prostate cancer (PCa), those with benign prostatic hyperplasia (BPH) and age-matched healthy male control subjects. Using a combination of 2DE and MS/MS, significantly lower expression of urinary saposin B and two different fragments of inter-alpha-trypsin inhibitor light chain (ITIL) was demonstrated in the PCa patients compared to the controls. However, only one of the ITIL fragments was significantly different between the PCa and BPH patients. When image analysis was performed on urinary proteins that were transferred onto NC membranes and detected using a lectin that binds to O-glycans, a truncated fragment of inter-alpha-trypsin inhibitor heavy chain 4 was the sole protein found to be significantly enhanced in the PCa patients compared to the controls. Together, these urinary peptide fragments might be useful complementary biomarkers to indicate PCa as well as to distinguish it from BPH, although further epidemiological evidence on the specificity and sensitivity of the protein candidates is required.

  15. Role of Circulating CD4+ CD25high Foxp3+ Regulatory T-Cells in Paediatric Asthma

    Directory of Open Access Journals (Sweden)

    Ensaf Khalil Mohammed*, Zeinab Farag Asheiba

    2011-04-01

    Full Text Available Background: The role of T-Helper 2 (Th2 cells in the pathogenesis of allergy and asthma has been well described. However, the immunologic mechanisms that down modulate and protect against the development of these disorders are poorly characterized. A spectrum of CD4+ T cells, including, FOXP3-positive CD4+CD25+ T regulatory cells (Tregs might play a critical role in regulating these diseases. Objective: To investigate the role of CD4+CD25high FoxP3 Tregs in the pathogenesis of pediatric asthma. Methods: The study included 24 asthmatic children, 12 had mild intermittent asthma and 12 were of severe persistent asthma . In addition, 12 healthy subjects were used as controls. All patients were subjected to clinical examination and laboratory investigations including complete blood count with differential leucocytic and absolute eosinophilic count, serum total IgE level by ELIZA and flow cytometry was used to study the frequency of Tregs in peripheral blood lymphocytes of all studied groups using specific markers: cell-surface CD25 and CD4 expression and cytoplasmic FoxP3 expression. Results: It was noticed a significant decrease in CD4+CD25+ % and CD4+CD25 high % in both mild intermittent cases and severe persistent asthmatic patients when compared to healthy controls. FoxP3 expression in Tregs was significantly lower in CD4+CD25high T-cells of mild asthmatic patients when compared to control group. While the FoxP3 expression in Tregs was non- significantly lower in CD4+CD25high T-cells of severe asthmatic patients .Tregs cells % was correlated significantly with mild asthma .While it did not show correlation with severe asthma . An inverse correlation between FoxP3 protein expression was revealed within CD4+CD25high T-cells and total serum IgE when analyzed for all subjects. However, when correlation analysis was performed in each studied group separately, no significant correlation was found between FoxP3 expression and total serum IgE levels and

  16. CD4(+CD25(-Nrp1(+ T cells synergize with rapamycin to prevent murine cardiac allorejection in immunocompetent recipients.

    Directory of Open Access Journals (Sweden)

    Qing Yuan

    Full Text Available Besides CD4(+CD25(+Foxp3(+ regulatory T cells (Tregs, other immunosuppressive T cells also participated in the regulation of immune tolerance. Reportedly, neuropilin-1 (Nrp1 might be one of the molecules by which regulatory cells exert their suppressive effects. Indeed, CD4(+CD25(-Nrp1(+ T cells exhibit potent suppressive function in autoimmune inflammatory responses. Here we investigated the specific role of CD4(+CD25(-Nrp1(+ T cells in the setting of the transplant immune response. Through MLR assays, we found that CD4(+CD25(-Nrp1(+ T cells suppressed the proliferation of naive CD4(+CD25(- T cells activated by allogeneic antigen-stimulation. Adoptive transfer of CD4(+CD25(-Nrp1(+ T cells synergized with rapamycin to induce long-term graft survival in fully MHC-mismatched murine heart transplantation, which was associated with decreased IFN-γ, IL-17 and increased IL-10, TGF-β, Foxp3 and Nrp1 expression in the grafts. Importantly, our data indicated that CD4(+CD25(-Nrp1(+ T cell transfer augments the accumulation of Tregs in the recipient, and creates conditions that favored induction of hyporesponsiveness of the T effector cells. In conclusion, this translational study indicates the possible therapeutic potential of CD4(+CD25(-Nrp1(+ T cells in preventing allorejection. CD4(+Nrp1(+ T cells might therefore be used in bulk as a population of immunosuppressive cells with more beneficial properties concerning ex vivo isolation as compared to Foxp3(+ Tregs.

  17. CD4 + CD25 + Treg cell separate, phenotype identity and Foxp3 gene expression identity%CD4+CD25+Treg细胞的分选、表型鉴定及Foxp3表达鉴定

    Institute of Scientific and Technical Information of China (English)

    韩文杰; 史艳侠

    2010-01-01

    目的 为验证从C57BL/6小鼠脾脏中分离出高纯度CD4+CD25+Treg细胞及证实CD4+CD25+Treg细胞中Foxp3基因的表达.方法 使用免疫磁珠分选出CD4+CD25+Treg细胞,流式细胞仪检测纯度;使用TRIZOL抽提Foxp3基因mRNA,使用RT-PCR方法逆转录出Foxp3基因的cDNA.结果 从C57BL/6小鼠脾脏中分离出了纯度达到90%CD4+CD25+Treg.进一步应用RT-PCR技术克隆出Foxp3的cDNA,通过凝胶电泳证实了克隆出了Foxp3的cDNA.结论 使用免疫磁珠方法能够分离出C57BL/6小鼠CD4+CD25+Treg细胞,并进行了Foxp3基因表达的鉴定.%Objective To confirm high purity CD4 + CD25 + Treg cells can be separated from the spleen of C57BL/6 mice and Foxp3 gene can be express in CD4 + CD25 + Treg cells.Methods CD4 + CD25 + Treg cells are separated with immunomagnetic beads,and purity is detected by flow cytometry.Foxp3 gene mRNA is extracted using TRIZOL.Foxp3 gene cDNA is reverse transcription using RT-PCR technology.Results This study separated CD4 + CD25 + Treg cell of 90% purity from the spleen of C57BI/6 mice,to advance used technology of RT-PCR to make the clone of Foxp3 gene cDNA,and confirmed it is the cDNA of foxp3.Conclusion This study CD4 + CD25 + Treg cell can be separated from the spleen of C57BL/6 mice with immnnomagnetic beads,and identified foxp3 gene expression.

  18. Naturally Occurring Self-Reactive CD4+CD25+ Regulatory T Cells: Universal Immune Code

    Institute of Scientific and Technical Information of China (English)

    Nafiseh Pakravan; Agheel Tabar Molla Hassan; Zuhair Muhammad Hassan

    2007-01-01

    Naturally occurring thymus-arisen CD4+CD25+ regulatory T (Treg) cells are considered to play a central role in self-tolerance. Precise signals that promote the development of Treg cells remain elusive, but considerable evidence suggests that costimulatory molecules, cytokines, the nature of the TCR and the niche or the context in which the T cell encounters antigen in the thymus play important roles. Analysis of TCR from Treg cells has demonstrated that a large proportion of this population has a higher avidity to self-antigen in comparison with TCR from CD4+CD25- cells and that peripheral antigen is required for their development, maintenance, or expansion. Treg cells have been shown to undergo expansion in the periphery, likely regulated by the presence of self-antigen. Many studies have shown that the involvement of Treg cells in the tolerance induction is antigen-specific, even with MHC-mismatched,in transplantation/graft versus host disease (GVHD), autoimmunity, cancer, and pregnancy. Theses studies concluded a vital role for self-reactive Treg cells in maintenance of the body integrity. Based on those studies, we hypothesize that self-reactive Treg cells are shared among all healthy individuals and recognize same self-antigens and their TCR encodes for few dominant antigens of each organ which defines the healthy self. These dominant self antigens can be regarded as "universal immune code".

  19. Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells

    Science.gov (United States)

    Yessoufou, Akadiri; Plé, Aude; Moutairou, Kabirou; Hichami, Aziz; Khan, Naim Akhtar

    2009-01-01

    Immunological tolerance is one of the fundamental aspects of the immune system. The CD4+CD25+ regulatory T (Treg) cells have emerged as key players in the development of tolerance to self and foreign antigens. However, little is known about the endogenous factors and mechanisms controlling their suppressive capacity on immune response. In this study, we observed that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, diminished, in a dose-dependent manner, the capacity of Treg cells to inhibit the CD4+CD25− effector T-cell proliferation. DHA not only reduced the migration of Treg cells toward chemokines but also downregulated the mRNA expression of CCR-4 and CXCR-4 in Treg cells. DHA also curtailed ERK1/2 and Akt phosphorylation and downregulated the Smad7 levels in these cells. Contradictorily, DHA upregulated the mRNA expression of Foxp3, CTLA-4, TGF-β, and IL-10; nonetheless, this fatty acid increased the expression of p27KIP1 mRNA, known to be involved in Treg cell unresponsiveness. In Foxp3-immunoprepitated nuclear proteins, DHA upregulated histone desacetylase 7 levels that would again participate in the unresposnsiveness of these cells. Finally, a DHA-enriched diet also diminished, ex vivo, the suppressive capacity of Treg cells. Altogether, these results suggest that DHA, by diminishing Treg cell functions, may play a key role in health and disease. PMID:19561360

  20. Side-chain-anchored N(alpha)-Fmoc-Tyr-OPfp for bidirectional solid-phase synthesis

    DEFF Research Database (Denmark)

    Olsen, Christian A; Jørgensen, Malene; Hansen, Steen H;

    2005-01-01

    [reaction: see text] A mild resin-immobilization strategy employing a readily prepared trityl bromide resin for anchoring building blocks via a phenol group has been developed. With N(alpha)-Fmoc-Tyr-OPfp as a starter building block, it was possible to prepare asymmetrically substituted hybrids o...... of spider- and wasp-type polyamine toxins using solid-phase peptide synthesis conditions....

  1. Affinity purification of human granulocyte macrophage colony-stimulating factor receptor alpha-chain. Demonstration of binding by photoaffinity labeling

    International Nuclear Information System (INIS)

    The human granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain, a low affinity component of the receptor, was solubilized and affinity-purified from human placenta using biotinylated GM-CSF. Scatchard analysis of 125I-GM-CSF binding to the placental membrane extract disclosed that the GM-CSF receptor had a dissociation constant (Kd) of 0.5-0.8 nM, corresponding to the Kd value of the GM-CSF receptor alpha-chain on the intact placental membrane. Affinity labeling of the solubilized protein using a photoreactive cross-linking agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), demonstrated a single specific band of 70-95 kDa representing a ligand-receptor complex. Approximately 2 g of the placental membrane extract was subjected to a biotinylated GM-CSF-fixed streptavidin-agarose column, resulting in a single major band at 70 kDa on a silver-stained sodium dodecyl sulfate gel. The radioiodination for the purified material disclosed that the purified protein had an approximate molecular mass of 70 kDa and a pI of 6.6. Binding activity of the purified material was demonstrated by photoaffinity labeling using HSAB-125I-GM-CSF, producing a similar specific band at 70-95 kDa as was demonstrated for the crude protein

  2. Affinity purification of human granulocyte macrophage colony-stimulating factor receptor alpha-chain. Demonstration of binding by photoaffinity labeling

    Energy Technology Data Exchange (ETDEWEB)

    Chiba, S.; Shibuya, K.; Miyazono, K.; Tojo, A.; Oka, Y.; Miyagawa, K.; Takaku, F. (Univ. of Tokyo (Japan))

    1990-11-15

    The human granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain, a low affinity component of the receptor, was solubilized and affinity-purified from human placenta using biotinylated GM-CSF. Scatchard analysis of {sup 125}I-GM-CSF binding to the placental membrane extract disclosed that the GM-CSF receptor had a dissociation constant (Kd) of 0.5-0.8 nM, corresponding to the Kd value of the GM-CSF receptor alpha-chain on the intact placental membrane. Affinity labeling of the solubilized protein using a photoreactive cross-linking agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), demonstrated a single specific band of 70-95 kDa representing a ligand-receptor complex. Approximately 2 g of the placental membrane extract was subjected to a biotinylated GM-CSF-fixed streptavidin-agarose column, resulting in a single major band at 70 kDa on a silver-stained sodium dodecyl sulfate gel. The radioiodination for the purified material disclosed that the purified protein had an approximate molecular mass of 70 kDa and a pI of 6.6. Binding activity of the purified material was demonstrated by photoaffinity labeling using HSAB-{sup 125}I-GM-CSF, producing a similar specific band at 70-95 kDa as was demonstrated for the crude protein.

  3. Cloning of the laminin {alpha}3 chain gene (LAMA3) and identification of a homozygous deletion in a patient with Herlitz junctional epidermolysis bullosa

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, F.; Ortonne, J.P. [INSERM, Nice (France)]|[Hospital Pasteur, Nice (France); Galliano, M.F. [INSERM, Nice (France)] [and others

    1995-11-20

    Laminin 5 and laminin 6 are basement membrane proteins synthesized by the basal cells of stratifying squamous epithelia. Altered expression of laminin 5 has been associated with Herlitz junctional epidermolysis bullosa (H-JEB), a severe epidermal blistering disorder inherited as an autosomal recessive disease. We have isolated cDNA clones encoding the {alpha}3 chain of laminin 5 and searched for mutations in the LAMA3 gene in H-JEB patients. In one H-JEB family, an affected individual exhibited drastically reduced immunoreactivity to antibodies directed against the {alpha}3 chain of laminin 5 and an impaired expression of the corresponding mRNA transcripts. RT-PCR analysis of mRNA extracted from the proband`s keratinocytes identified a homozygous single basepair deletion in the transcripts encoding the laminin {alpha}3A and {alpha}3B isoforms. The mutation causes a frameshift and premature termination codon in both alleles of the LAMA3 gene. Inheritance of the clinical H-JEB phenotype was consistent with the segregation of the mutated allele in the family. We also report the identity of the {alpha} chains of laminin 5 and epiligrin and provide evidence that LAMA3 transcripts are distinct from the laminin 6 {alpha} chain mRNA. 35 refs., 5 figs., 1 tab.

  4. Cloning of the laminin alpha 3 chain gene (LAMA3) and identification of a homozygous deletion in a patient with Herlitz junctional epidermolysis bullosa.

    Science.gov (United States)

    Vidal, F; Baudoin, C; Miquel, C; Galliano, M F; Christiano, A M; Uitto, J; Ortonne, J P; Meneguzzi, G

    1995-11-20

    Laminin 5 and laminin 6 are basement membrane proteins synthesized by the basal cells of stratifying squamous epithelia. Altered expression of laminin 5 has been associated with Herlitz junctional epidermolysis bullosa (H-JEB), a severe epidermal blistering disorder inherited as an autosomal recessive disease. We have isolated cDNA clones encoding the alpha 3 chain of laminin 5 and searched for mutations in the LAMA3 gene in H-JEB patients. In one H-JEB family, an affected individual exhibited drastically reduced immunoreactivity to antibodies directed against the alpha 3 chain of laminin 5 and an impaired expression of the corresponding mRNA transcripts. RT-PCR analysis of mRNA extracted from the proband's keratinocytes identified a homozygous single basepair deletion in the transcripts encoding the laminin alpha 3A and alpha 3B isoforms. The mutation causes a frameshift and premature termination codon in both alleles of the LAMA3 gene. Inheritance of the clinical H-JEB phenotype was consistent with the segregation of the mutated allele in the family. We also report the identity of the alpha chains of laminin 5 and epiligrin and provide evidence that LAMA3 transcripts are distinct from the laminin 6 alpha chain mRNA. PMID:8586427

  5. CD4+CD25+ regulatory T cell depletion modulates anxiety and depression-like behaviors in mice.

    Directory of Open Access Journals (Sweden)

    Soo-Jeong Kim

    Full Text Available Stress has been shown to suppress immune function and increase susceptibility to inflammatory disease and psychiatric disease. CD4(+CD25(+ regulatory T (Treg cells are prominent in immune regulation. This study was conducted to determine if anti-CD25 antibody (Ab mediated depletion of Treg cells in mice susceptibility to stress-induced development of depression-like behaviors, as well as immunological and neurochemical activity. To accomplish this, an elevated plus-maze test (EPM, tail suspension test (TST, and forced swim test (FST were used to examine depression-like behaviors upon chronic immobilization stress. Immune imbalance status was observed based on analysis of serum cytokines using a mouse cytometric bead array in conjunction with flow cytometry and changes in the levels of serotonin (5-HT and dopamine (DA in the brain were measured by high performance liquid chromatography (HPLC. The time spent in the open arms of the EPM decreased significantly and the immobility time in the FST increased significantly in the anti-CD25 Ab-treated group when compared with the non stressed wild-type group. In addition, interlukin-6 (IL-6, tumor necrosis factor-á (TNF-á, interlukin-2 (IL-2, interferon-gamma (IFN-γ, interlukin-4 (IL-4 and interlukin-17A (IL-17A concentrations were significantly upregulated in the stressed anti-CD25 Ab-treated group when compared with the non stressed wild-type group. Furthermore, the non stressed anti-CD25 Ab-treated group displayed decreased 5-HT levels within the hippocampus when compared with the non stressed wild-type group. These results suggest that CD4(+CD25(+ Treg cell depletion modulated alterations in depressive behavior, cytokine and monoaminergic activity. Therefore, controlling CD4(+CD25(+ Treg cell function during stress may be a potent therapeutic strategy for the treatment of depression-like symptoms.

  6. Chemokines involved in protection from colitis by CD4+CD25+ regulatory T cells

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Brudzewsky, Dan; Gad, Monika;

    2006-01-01

    , the authors found down regulation of the mRNA expression of the inflammatory chemokine receptors CCR1 and CXCR3 and their ligands CXCL9, CXCL10, CCL5, and CCL7. Also the transcripts for CCR9, CCL25, CCL17, and CXCL1 are found down regulated in protected compared with colitic animals. In addition, the authors......' results suggest that CCL20 is used by CCR6 regulatory T cells in the complex process of controlling colitis because transcripts for this chemokine were expressed to a higher level in protected animals. The chemokine pathways identified in the present study may be of importance for the development of new....../chemokine receptor-specific gene expression profiling system of 67 genes, the authors have determined the expression profile of chemokine and chemokine receptor genes in the rectum of colitic mice and in mice that have been protected fromcolitis by CD4CD25 regulatory T cells. In mice protected from colitis...

  7. Structural requirements for assembly of dimeric IgA probed by site-directed mutagenesis of J chain and a cysteine residue of the alpha-chain CH2 domain.

    Science.gov (United States)

    Krugmann, S; Pleass, R J; Atkin, J D; Woof, J M

    1997-07-01

    The structural features of J chain required for interaction with IgA in IgA dimer assembly were investigated by coexpression of wild-type and mutant forms of J chain with IgA1 in CHO cells. With wild-type J chain, a mixture of J chain-containing dimers and monomers was secreted. Substitution of Cys14 of J chain with Ser resulted in expression of only monomer IgA covalently associated with J chain. Similarly, mutation of Cys68 to Ser also resulted in expression predominantly of a monomer IgA-J chain species. These results suggest that Cys14 and Cys68 play critical roles in formation of J chain-containing IgA dimers, with each forming a disulfide bridge to an IgA monomer. Substitution of Asn48 with Ala, to prevent attachment of N-linked carbohydrate to J chain, also resulted in markedly reduced dimer assembly, suggesting a requirement for the sugar moiety in J chain function. We also mutated Cys311 on the C alpha2 domain of the IgA heavy chain to Ser. When coexpressed with wild-type J chain, this mutant was still capable of forming dimers, indicating that this residue was not involved in dimerization. Taken together, our results are consistent with an arrangement in which IgA monomers are linked end-to-end with J chain interposed. PMID:9200460

  8. Human CD4+ CD25+ Foxp3+ regulatory T cells do not constitutively express IL-35.

    Science.gov (United States)

    Bardel, Emilie; Larousserie, Frédérique; Charlot-Rabiega, Pascaline; Coulomb-L'Herminé, Aurore; Devergne, Odile

    2008-11-15

    EBV-induced gene 3 (EBI3) can associate with p28 to form the heterodimeric cytokine IL-27, or with the p35 subunit of IL-12 to form the EBI3/p35 heterodimer, recently named IL-35. In mice, IL-35 has been shown to be constitutively expressed by CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells) and suggested to contribute to their suppressive activity. In this study, we investigated whether human Treg cells express IL-35. Double-staining analysis of human thymuses showed that neither Foxp3(+) nor CD25(+) cells coexpressed EBI3. Similarly, Foxp3(+) cells present in human lymph nodes, tonsils, spleens, and intestines did not express EBI3. Consistent with these in situ observations, Treg cells purified from blood or tonsils were negative for EBI3 by immunoblotting. Other human T cell subsets, including effector T cells, naive and memory CD4(+) T cells, CD8(+) and gammadelta T cells also did not constitutively express EBI3, which contrasts with IL-35 expression observed in murine CD8(+) and gammadelta T cells. Furthermore, although CD3/CD28 stimulation consistently induced low levels of EBI3 in various CD4(+) T cell subsets, no EBI3 could be detected in CD3/CD28-stimulated Treg cells. RT-PCR analysis showed that, whereas p35 transcripts were detected in both Teff and Treg cells, EBI3 transcripts were detected only in activated Teff cells, but not in resting or activated Treg cells. Thus, in contrast to their murine counterpart, human Treg cells do not express detectable amounts of IL-35.

  9. Theoretical study on the properties of new nuclide sup 2 sup 7 sup 1 110 and its alpha-decay chain

    CERN Document Server

    Ren Zhong Zhou

    2002-01-01

    The structures of the nuclei on the alpha decay chain of sup 2 sup 7 sup 1 110 are investigated using self-consistent relativistic mean-field (RMF) model. The calculated alpha-decay energies are in good agreement with experimental data. The theoretical lifetimes reasonably agree with the data. The properties of sup 2 sup 7 sup 5 112 are predicted. A discussion on the deformed shell around Z = 108 is made

  10. 白癜风患者外周血CD4+CD25+调节性T细胞的检测%Detection of peripheral CD4+CD25+ regulatory T lymphocytes in patients with vitiligo

    Institute of Scientific and Technical Information of China (English)

    白明辉; 王竞; 涂彩霞; 张蕴颖; 刘敏; 李国艳; 钟良瑞

    2009-01-01

    Objective To determine the level of peripheral CD4+CD25+ regulatory T lymphocytes in patients with vitiligo at different stages and to study its relationship with the development of vitiligo. Methods Blood samples were collected from 34 outpatients with vitiligo, including 19 cases of progressive vitiligo and 15 cases of stable vitiligo, as well as from 20 normal human controls. Flow cytometry was used to detect the levels of peripheral CD4+ and CD4+CD25+ T lymphocytes in these samples. Results Compared with the controls, the percentage of CD4+CD25+ regulatory T lymphoeytes in peripheral lymphocytes was significantly lower in patients with progressive vitiligo than those in patients with stable vitiligo and normal human con-trois [(2.43±0.30)% vs (3.49±0.39)% and (3.34±0.24)%, both P <0.05], but no significant difference was found between patients with stable vitiligo and normal human controls (P>0.05). A significantly nega-tive correlation was observed between the percentage of CD4+CD25+ regulatory T lymphocytes and lesion area in patients with progressive vitiligo (r = -0.48, P <0.05), but not in patients with stable vitiligo (P >0.05). There was no significant correlation between the course of disease and the percentage of peripheral CD4+CD25+ regulatory T lymphocytes in patients with progressive vitiligo or stable vitiligo (both P > 0.05). Conclusion There is an abnormal proportion of peripheral CD4+CD25+ regulatory T lymphocytes in patients with vitiligo, which may be related to the development of vitiligo.%目的 检测不同病期白癜风患者外周血CD4+CD25+调节性T细胞水平,探讨其与白癜风发病的关系.方法 白癜风患者34例,进展期19例,稳定期15例.通过流式细胞仪对不同病期白癜风患者外周血CD4+、CD4+CD25+T细胞水平进行检测,并与20例正常人比较.结果 进展期患者外周血中CD4+CD25+调节性T细胞占外周血淋巴细胞的表达率低于正常对照组(P<0.05);稳定期患者与正

  11. CD4+CD25+T调节细胞及Foxp3在哮喘中的研究进展%Research Progress of CD4+CD25+T Regulatory Cells and Foxp3 in Children with Asthma

    Institute of Scientific and Technical Information of China (English)

    王娜; 孔宪明; 曹兰芳

    2006-01-01

    CD4+CD25+T调节细胞是具有免疫调节(或抑制)作用的T细胞,其主要功能是抑制自身反应性T细胞的活化和增殖,参与自身免疫调节,维持自身免疫耐受,在儿童哮喘等疾病中发挥重要作用.Foxp3已作为CD4+CD25+T调节细胞的特异性标志.本文就CD4+CD25+T调节细胞及Foxp3的生物学特性、效应机制及其与儿童哮喘发病的关系作一综述.

  12. Ground State Properties of New Element Z = 113 and Its Alpha Decay Chain

    Institute of Scientific and Technical Information of China (English)

    TAI Fei; CHEN Ding-Han; XU Chang; REN Zhong-Zhou

    2005-01-01

    @@ We investigate the ground state properties of the new element 278113 and of the α-decay chain with different models, where the new element Z = 113 has been produced at RIKEN in Japan by cold-fusion reaction [Morita et al.J.Phys.Soc.Jpn.73 (2004) 2593].The experimental decay energies are reproduced by the deformed relativistic mean-field model, by the Skyrme-Hartree-Fock (SHF) model, and by the macroscopic-microscopic model.Theoretical half-lives also reasonably agree with the data.Calculations further show that prolate deformation is important for the ground states of the nuclei in the α-decay chain of 278113.The common points and differences among different models are compared and discussed.

  13. Fetal antigen 2: an amniotic protein identified as the aminopropeptide of the alpha 1 chain of human procollagen type I

    DEFF Research Database (Denmark)

    Teisner, B; Rasmussen, H B; Højrup, P;

    1992-01-01

    -PAGE analysis gave an M(r) = 27 kDa under reducing and non-reducing conditions for both forms, whereas the exact M(r) determined by mass spectrometry was 14,343 +/- 3 Da. FA2 was N-terminally blocked and after tryptic digestion the amino acid composition and sequences of the peptides showed identity...... with the aminopropeptide of the alpha 1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio-iodination (iodogen and chloramine-T), FA2 lost its immunoreactivity. An antigen which cross-reacted with polyclonal rabbit anti-human FA2 was demonstrated...... in fetal calf serum. Gel filtration with analysis of fractions by inhibition ELISA showed that the bovine homologue was present in the same molecular forms as those in human amniotic fluid, and immunohistochemical analysis with anti-human FA2 showed that its distribution in bovine skin was identical...

  14. CD4+CD25+调节T细胞与肿瘤免疫治疗策略%CD4+CD25+Regulatory T Cells and Cancer Immunotherapy Strategy

    Institute of Scientific and Technical Information of China (English)

    白平; 王春晖

    2008-01-01

    随着分子生物技术的不断发展,肿瘤的生物治疗在临床应用中的地位日渐突出,其中CD4+CD25+Foxp3+调节T细胞(CD4+CD25+Foxp3+regulatory T cell,Treg)在抑制肿瘤免疫方面起着重要作用,文章就其近年来在肿瘤免疫领域的研究进展作一综述.

  15. Th17/CD4+CD25+Treg细胞与自身免疫病

    Institute of Scientific and Technical Information of China (English)

    王琴; 崔向军

    2011-01-01

    CD4+CD25+调节T细胞(CD4+CD25+Treg)是调节性T细胞的一个重要亚类,Treg可以通过IL-2、TGF-β1等促炎症细胞因子调节Th17/Treg平衡,调控Thl7细胞介导的炎症反应、自身免疫反应。本文将Thl7细胞/CD4+CD25+Treg细胞与自身免疫性疾病的关系作一综述。

  16. Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

    Science.gov (United States)

    Mayer, Elisabeth; Bannert, Christina; Gruber, Saskia; Klunker, Sven; Spittler, Andreas; Akdis, Cezmi A.

    2012-01-01

    Background: Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these “excessive” responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself. Methods: Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([3H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4+CD25highFoxP3+ T cells were characterized by mRNA analysis and flow cytometry. Results: Cord blood derived CD4+CD25high cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4+CD25high cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3+CD4+CD25highcells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4+CD25+CD127low) is highly suppressive even without prior antigen exposure. Conclusion: Cord blood harbors a very small subset of CD4+CD25high Treg cells that requires antigen-stimulation to show expansion and become functional suppressive Tregs. PMID:22272233

  17. Human and Mouse CD8+CD25+FOXP3+ Regulatory T Cells at Steady State and during Interleukin-2 Therapy

    OpenAIRE

    Churlaud, Guillaume; Pitoiset, Fabien; Jebbawi, Fadi; Lorenzon, Roberta; Bellier, Bertrand; Rosenzwajg, Michelle; Klatzmann, David

    2015-01-01

    International audience In addition to CD4+ regulatory T cells (Tregs), CD8+ suppressor T cells are emerging as an important subset of regulatory T cells. Diverse populations of CD8+ T cells with suppressive activities have been described. Among them, a small population of CD8+CD25+FOXP3+ T cells is found both in mice and humans. In contrast to thymic-derived CD4+CD25+FOXP3+ Tregs, their origin and their role in the pathophysiology of autoimmune diseases (AIDs) are less understood. We repor...

  18. Role of Circulating CD4+ CD25high Foxp3+ Regulatory T-Cells in Paediatric Asthma

    OpenAIRE

    Ensaf Khalil Mohammed*, Zeinab Farag Asheiba

    2011-01-01

    Background: The role of T-Helper 2 (Th2) cells in the pathogenesis of allergy and asthma has been well described. However, the immunologic mechanisms that down modulate and protect against the development of these disorders are poorly characterized. A spectrum of CD4+ T cells, including, FOXP3-positive CD4+CD25+ T regulatory cells (Tregs) might play a critical role in regulating these diseases. Objective: To investigate the role of CD4+CD25high FoxP3 Tregs in the pathogenesis of pediatric ast...

  19. Defects in very long chain fatty acid synthesis enhance alpha-synuclein toxicity in a yeast model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Yong Joo Lee

    Full Text Available We identified three S. cerevisiae lipid elongase null mutants (elo1Δ, elo2Δ, and elo3Δ that enhance the toxicity of alpha-synuclein (α-syn. These elongases function in the endoplasmic reticulum (ER to catalyze the elongation of medium chain fatty acids to very long chain fatty acids, which is a component of sphingolipids. Without α-syn expression, the various elo mutants showed no growth defects, no reactive oxygen species (ROS accumulation, and a modest decrease in survival of aged cells compared to wild-type cells. With (WT, A53T or E46K α-syn expression, the various elo mutants exhibited severe growth defects (although A30P had a negligible effect on growth, ROS accumulation, aberrant protein trafficking, and a dramatic decrease in survival of aged cells compared to wild-type cells. Inhibitors of ceramide synthesis, myriocin and FB1, were extremely toxic to wild-type yeast cells expressing (WT, A53T, or E46K α-syn but much less toxic to cells expressing A30P. The elongase mutants and ceramide synthesis inhibitors enhance the toxicity of WT α-syn, A53T and E46K, which transit through the ER, but have a negligible effect on A30P, which does not transit through the ER. Disruption of ceramide-sphingolipid homeostasis in the ER dramatically enhances the toxicity of α-syn (WT, A53T, and E46K.

  20. CD4+CD25+调节性T细胞在心脏疾病中的研究进展%The Research Progress of CD4 +CD25 + Regulatory T Cells in Heart Diseases

    Institute of Scientific and Technical Information of China (English)

    牛瑞兵

    2011-01-01

    CD4+ CD25+ regulatory T cells( Treg ) are a special subgroup of T cells in vivo with an immunoregulatory function. In recent years, massive domestic and oversea research indicated that Treg is closely related with various cardiovascular disease's occurrence and development. Therefore, understanding of Treg and its immunosuppression's mechanism in the heart disease is helpful to improve the immunotherapy effect for heart diseases. Here is to make a summary of CD4+ CD25 + Treg' production, features, functional mechanism and its correlation with heart diseases.%CD4 +CD25 +调节性T细胞(Treg)是体内具有免疫调节功能的一类特殊T细胞亚群.近年来,国内外的大量研究表明Treg与很多种心血管疾病的发生和进展密切相关.因此,认识Treg及其在心脏疾病中免疫抑制的机制,有助于提高心脏疾病的免疫治疗效果.现就CD4 +CD25 +Treg的产生、特征、作用机制及其与心脏疾病的联系予以综述.

  1. CD4+CD25+调节性T细胞在支气管哮喘中的研究进展%Changes and effects of CD4+CD25+ regulatory T cells in pathogenesis of asthma

    Institute of Scientific and Technical Information of China (English)

    宋丽; 施森; 李敏

    2007-01-01

    近年来,关于CD4+CD25+调节性T细胞在支气管哮喘发病中作用的研究有相当大的进展,支气管哮喘的发病机制已不能单纯用Th1/Th2平衡理论来解释,CD4+CD25+调节性T细胞越来越受到重视,它通过细胞接触和分泌细胞因子发挥免疫抑制功能,维持自身免疫平衡,控制支气管哮喘的发展,Foxp3、IL-6等在其功能调控中发挥重要作用.支气管哮喘中,有关CD4+CD25+调节性T细胞作用机制及数量变化的观点不一,糖皮质激素通过增强CD4+CD25+调节性T细胞功能发挥治疗作用.

  2. Creatine, arginine alpha-ketoglutarate, amino acids, and medium-chain triglycerides and endurance and performance.

    Science.gov (United States)

    Little, Jonathan P; Forbes, Scott C; Candow, Darren G; Cornish, Stephen M; Chilibeck, Philip D

    2008-10-01

    Creatine (Cr) supplementation increases muscle mass, strength, and power. Arginine a-ketoglutarate (A-AKG) is a precursor for nitric oxide production and has the potential to improve blood flow and nutrient delivery (i.e., Cr) to muscles. This study compared a commercial dietary supplement of Cr, A-AKG, glutamine, taurine, branched-chain amino acids, and medium-chain triglycerides with Cr alone or placebo on exercise performance and body composition. Thirty-five men (approximately 23 yr) were randomized to Cr + A-AKG (0.1 g . kg(-1) . d(-1) Cr + 0.075 g . kg(-1) . d(-1)A-AKG, n = 12), Cr (0.1 g . kg(-1) . d(-1), n = 11), or placebo (1 g . kg(-1) . d(-1) sucrose, n = 12) for 10 d. Body composition, muscle endurance (bench press), and peak and average power (Wingate tests) were measured before and after supplementation. Bench-press repetitions over 3 sets increased with Cr + A-AKG (30.9 +/- 6.6 +/- 34.9 +/- 8.7 reps; p < .01) and Cr (27.6 +/- 5.9 +/- 31.0 +/- 7.6 reps; p < .01), with no change for placebo (26.8 +/- 5.0 +/- 27.1 +/- 6.3 reps). Peak power significantly increased in Cr + A-AKG (741 +/- 112 +/- 794 +/- 92 W; p < .01), with no changes in Cr (722 +/- 138 +/- 730 +/- 144 W) and placebo (696 +/- 63 +/- 705 +/- 77 W). There were no differences in average power between groups over time. Only the Cr-only group increased total body mass (79.9 +/- 13.0 +/- 81.1 +/- 13.8 kg; p < .01), with no significant changes in lean-tissue or fat mass. These results suggest that Cr alone and in combination with A-AKG improves upper body muscle endurance, and Cr + A-AKG supplementation improves peak power output on repeated Wingate tests. PMID:19033611

  3. [Hemoglobin Boumerdès alpha 2(37) (C2) Pro----Arg beta 2: a new variant of the alpha chain associated with hemoglobin S in an Algerian family].

    Science.gov (United States)

    Dahmane-Arbane, M; Blouquit, Y; Arous, N; Bardakdjian, J; Benamani, M; Riou, J; Benabadji, M; Rosa, J; Galacteros, F

    1987-01-01

    We report the first case of Hb Boumerdes, an alpha chain variant alpha 2(37) (C2) Pro----Arg beta 2, in an Algerian family. The propositus was also homozygous for the sickle cell gene. The abnormal hybrid Hb alpha 2Boum. beta 2S had an electrophoretic mobility on cellulose acetate pH 8.7 electrophoresis between those of Hb S and Hb A2. Its expression was about 16%. The alpha 2Boum. beta 2A fraction has a mobility between those of Hb F and Hb S. The effects of this mutation on Hb oxygen affinity and deoxy Hb S polymer formation were not studied. The propositus' sickle cell phenotype was benign. PMID:3438164

  4. Properties of Z=120 nuclei and the \\alpha-decay chains of the (292,304)120 isotopes using relativistic and non-relativistic formalisms

    CERN Document Server

    Ahamad, Shakeb; Patra, S K

    2012-01-01

    The ground state and first intrinsic excited state of superheavy nuclei with Z=120 and N=160-204 are investigated using both non-relativistic Skyrme-Hartree-Fock and the axially deformed Relativistic Mean Field formalisms. We employ a simple BCS pairing approach for calculating the energy contribution from pairing interaction. The results for isotopic chain of binding energy, quadrupole deformation parameter, two neutron separation energies and some other observables are compared with the FRDM and some recent macroscopic-microscopic calculations. We predict superdeformed ground state solutions for almost all the isotopes. Considering the possibility of magic neutron number, two different mode of \\alpha-decay chains (292)120 and (304)120 are also studied within these frameworks. The Q_{\\alpha}-values and the half-life T^{\\alpha}_{1/2} for these two different mode of decay chains are compared with FRDM and recent macroscopic-microscopic calculations. The calculation is extended for the \\alpha-decay chains of 29...

  5. FcR gamma-chain dependent signaling in immature Neutrophils is mediated by Fc alpha RI, but not by Fc gamma RI

    NARCIS (Netherlands)

    Otten, Marielle A.; Leusen, Jeanette H. W.; Rudolph, Esther; van der Linden, Joke A.; Beelen, Robert H. J.; de Winkel, Jan G. J. van; van Egmond, Marjolein

    2007-01-01

    Neutrophil-mediated tumor cell lysis is more efficiently triggered by Fc alpha RI (CD89), than by Fc gamma RI (CD64). This difference is most evident in immature neutrophils in which Fc gamma RI-mediated tumor cell lysis is absent. In this study, we show that FcR gamma-chain-dependent functions (suc

  6. CD4+CD25+调节性T细胞在Graves眼病患者外周血中的表达%Detection of CD4+CD25+regulatory T cell in patients with Graves'ophthalmopathy

    Institute of Scientific and Technical Information of China (English)

    辛梦; 王强; 张磊; 韩兆东; 薛海波

    2013-01-01

    AIM: To observe the change law of the ratio of CD4+CD25+regulatory T cell in the peripheral blood of the patients with Graves'ophthalmopathy by detecting the ratio of this cell. METHODS: This experimental study selected 53 GO patients without exophthalmos, 51 GO patients with exophthalmos, and 51 healthy people were collected.The ratio of CD4+CD25+ T cell in peripheral blood was determined by flow cytometry. RESULTS:The ratio of CD4+CD25+T cell in GO patients without exophthalmos was lower than that in healthy group (P<0.01).The ratio of CD4+CD25+T cell in GO patients with exophthalmos was far lower than that in healthy group (P<0.01).Compared with the group of GO patients without exophthalmos, the ratio of CD4+CD25+T cell of GO patients with exophthalmos was also much lower (P<0.01). CONCLUSION:The ratio of CD4+CD25+T cell in the GO patients decreases and there is autoimmune disorder in patients of this disease. Perhaps this is an important mechanism causing immune suppression damage, which provides a new clue for immunological treatment.%目的:通过检测CD4+CD25+调节性T细胞在Graves眼病患者外周血中的表达,以观察该病患者外周血中CD4+CD25+调节性T细胞的变化规律。方法:临床实验研究。采用流式细胞术检测对Graves病不伴有眼征患者组(53例), Graves眼病患者组(51例),正常对照组(51例)的外周静脉血CD4+CD25+Treg细胞比例进行检测。结果:与正常对照组比较, Graves 病不伴有眼征患者组Treg水平下降(P<0.01);与正常对照组比较,Graves眼病患者组外周血Treg水平显著下降( P<0.01);Graves眼病患者组外周血Treg数量明显低于Graves病不伴有眼征患者组(P<0.01)。结论:Graves眼病患者外周血中CD4+CD25+Treg在淋巴细胞中所占的比例降低,存在自身免疫调节紊乱。可能是其机体细胞免疫抑制受损的重要机制,为对该疾病进行免疫学治疗提供了新线索。

  7. Cutting edge: TNFR-shedding by CD4+CD25+ regulatory T cells inhibits the induction of inflammatory mediators.

    NARCIS (Netherlands)

    Mierlo, G.J. van; Scherer, H.U.; Hameetman, M.; Morgan, M.E.; Flierman, R.; Huizinga, T.W.J.; Toes, R.E.

    2008-01-01

    CD4+CD25+ regulatory T (Treg) cells play an essential role in maintaining tolerance to self and nonself. In several models of T cell-mediated (auto) immunity, Treg cells exert protective effects by the inhibition of pathogenic T cell responses. In addition, Treg cells can modulate T cell-independent

  8. The expression of tumor necrosis factor-a induced protein 8 like-2 in CD4+ CD25+ regulatory T cells%肿瘤坏死因子-α诱导蛋白-8样分子2在调节性T细胞中的表达

    Institute of Scientific and Technical Information of China (English)

    栾樱译; 姚咏明

    2011-01-01

    目的:观察肿瘤坏死因子-α诱导蛋白-8样分子2(TIPE2)在CD4CD25调节性T细胞(CD4CD25Treg)中的表达.方法:免疫磁珠法分离正常BALB/C小鼠脾脏CD4CD25Tregs,流式细胞术鉴定CD4CD25Treg的纯度.激光共聚焦荧光法检测Treg细胞中TIPE2的分布,并进行初步定位;进一步采用逆转录一聚合酶链反应(RT-PCR)和Western blot技术分别从基因和蛋白水平检测Treg细胞中TIPE2表达.结果:免疫磁珠分选法得到的CD4CD25Tregs纯度在92%以上,台盼蓝染色显示细胞活性大于97%.Western blot证实Treg细胞中存在清晰TIPE2条带,分子质量为21 kD;采用RT-PCR技术在Treg细胞中检测到147 bp大小的特异性TIPE2目的基因条带.结论:TIPE2可表达于小鼠CD4CD25Treg细胞.%Objective: To investigate the expression of tumor necrosis factor-α induced protein 8 like2 ( TIPF2)in CD4+ CD25+ regulatory T cells ( CD4+ CD25+ Tregs). Methods: CD4+ CD25+ Tregs were isolated from the spleens of male BALB/C mice by magnetic beads, and the purity of these cells was determined by flow cytometry.The present study was designed to determine TIPE2 expression in Tregs by confocal microscopy analysis, Western blot and reverse transcription-polymerase chain reaction ( RT-PCR) analysis, respectively. Results: Purity of CD4+ CD25+ Tregs was greater than 92%. The expression of TIPF2 was detected by confocal microscopy, and it was a cytoplasmic protein expressed in CD4+ CD25+Tregs. To confirm the expression of TIPF2 , it was detected by Western blot analysis using specific TIPF2 antibody, and a clear band with a molecular mass of approximately 21 kD from CD4+ CD25+ Tregs was found. Moreover, to determine the gene expression of TIPF2 , total RNA was extracted from CD4+ CD25+ Tregs and RT-PCR was performed, a band of the size of 147 bp was noted as expected. Conclution: TIPF2 appears to be a cytoplasmic protein expressed in CD4+ CD25+ Tregs.

  9. 佛波醇酯加离子霉素诱导脐血和成人外周血CD4+CD25+T细胞分泌IL-2的相关机制研究%Mechanisms underlying the induction of IL- 2 secretion by PDB plus ionomycin in CD4 + CD25 + T cells from cord blood and adult peripheral blood

    Institute of Scientific and Technical Information of China (English)

    肇静娴; 曾耀英; 李海仙; 曾祥凤; 季煜华; 何贤辉

    2006-01-01

    目的:以佛波醇酯加离子霉素作为刺激剂,验证CD4+CD25+调节性T细胞本身并不存在分泌IL-2障碍;同时通过对脐血和成人外周血的比较性研究,了解脐血CD4+CD25+T细胞的成熟度.方法:以autoMACS从足月婴儿脐血(CB)和成人外周血(PB)分选CD4+CD25+和CD4+CD25-T细胞,以PDB+ionomycin作为刺激剂,培养45h后流式细胞术检测各组细胞表达CD69和CD25水平,并以Luminex多重细胞因子检测技术检测培养上清中7种细胞因子的浓度.结果:经PDB+ionomycin刺激后,CB、PB的CD4+CD25+和CD4+CD25-T细胞均发生增殖,但在培养45h后CD4+CD25+T细胞均出现细胞状态变差或死亡倾向.CB、PB的CD4+CD25+T细胞活化后CD25分子表达进一步上调,高于CD25-细胞活化后的CD25分子密度.经PDB+ionomycin刺激后,PB CD4+CD25+和CD4+CD25-T细胞均分泌高水平的IFN-γ、IL-2和TNF-α,但CD25+细胞分泌IL-5、IL-4和IL-10水平远远高于CD25-细胞;CBCD4+CD25+和CD4+CD25-T细胞亦分泌高水平的IL-2和TNF-α,但IFN-γ水平远远低于PB,基本不分泌IL-5、IL-4和IL-10.结论:CD4+CD25+T细胞本身并不存在合成和分泌IL-2障碍,其可能具有与传统T细胞不同的T细胞受体信息转导模式;脐血CD4+CD25+T细胞功能尚未完全成熟.

  10. Shen-Qi-Jie-Yu-Fang exerts effects on a rat model of postpartum depression by regulating inflammatory cytokines and CD4+CD25+ regulatory T cells

    Science.gov (United States)

    Li, Jingya; Zhao, Ruizhen; Li, Xiaoli; Sun, Wenjun; Qu, Miao; Tang, Qisheng; Yang, Xinke; Zhang, Shujing

    2016-01-01

    Background Shen-Qi-Jie-Yu-Fang (SJF) is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD). Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4+CD25+ regulatory T (Treg) cells. Materials and methods Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of Treg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL)-1β and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1RI, IL-6Rα, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results Serum IL-1β in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1β and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1RI and gp130 in PPD rats were consistent with changes in serum IL-1β, and were able to be regulated by SJF and fluoxetine. The levels of Treg cells were negatively correlated with serum IL-1β and IL-6, and were decreased in PPD rats. The levels of Treg cells were increased by SJF and fluoxetine. Conclusion Dysfunction of proinflammatory cytokines and Tregs in different stages of PPD was attenuated by SJF and fluoxetine through the modulation of serum concentrations of IL-1β and IL-6, expressions of IL-1RI, and gp130 in the hippocampus, and CD4+CD25+ Treg cells in peripheral blood. PMID:27143890

  11. CD4~+ CD25~+调节性T细胞对哮喘大鼠气道炎症的影响%The effects of CD4~+ CD25~+ regulatory T cells on the airway inflammation of asthmatic rats

    Institute of Scientific and Technical Information of China (English)

    薛克营; 王成国; 程立; 杨中卫; 王正艳; 李威; 石明; 唐友勇

    2009-01-01

    目的 观察CD4~+CD25~+调节性T细胞(CD4~+CD25~+Treg)对哮喘大鼠气道炎症的影响.方法 将卵白蛋白(OVA)免疫耐受大鼠CD4+CD25~+Treg细胞过继转移给哮喘大鼠,然后观察支气管肺泡灌洗液(BALF)中细胞计数及分类,ELISA检测BALF中IL-4、IL-5和IFN-γ及血清OVA特异性IgE含量,HE染色观察肺组织的病理改变.结果 与哮喘组比较,过继转移CD4~+CD25~+ Treg细胞后哮喘大鼠BALF中细胞总数、中性粒细胞和淋巴细胞百分率降低(P<0.05),嗜酸性粒细胞(Eos)百分率明显降低(P<0.01);BALF中IL-4和IL-5含量明显降低,IFN-γ含量明显升高,血清OVA特异性IgE含量明显降低(P<0.05);气道炎症明显减轻.结论 过继转移OVA免疫耐受大鼠CD4~+CD25~+ Treg细胞可以明显抑制哮喘的慢性气道炎症.%Objective To observe the effects of CD4~+ CD25~+ regulatory T cells ( CD4~+ CD25~+ Treg) on the airway inflammation of asthmatic rats. Methods CD4~+ CD25~+ Treg of OVA- immune tolerance rats were transferred to asthmatic rats. Then bronchoalveolar lavage fluid (BALF) was collected, and cytology study was conducted. The IL-4, IL-5, IFN-γ and OVA-specific serum IgE level in BALF were determined by ELISA. The lung tissue was obtained, and histologieal analysis was done through H. E. Results Total cells number, the percentage of lymphocytes and neutrophils in BALF, the IL-4 and IL-5 BALF levels and the OVA-specific serum IgE level of adoptive transfer group were decreased ( P < 0.05 ) , and the percentage of eosinophils ( Eos) was significantly lower than that of asthma group ( P < 0.01) , while its BALF IFN-γ level was higher than that of asthma group( P <0. 05). Compared with that of asthma group, peribronchiole inflammatory of treated group was alleviated. Conclusion CD4 ~+ CD25~+ Treg of OVA- immune tolerance rats transferred to asthmatic rats can significantly alleviate the airway inflammation of asthmatic rats.

  12. 吸毒人员外周血CD4+CD25+Foxp3调节性T细胞表达%Expression of CD4+CD25+Foxp3 regulatory T cells in the blood of drug abuse population

    Institute of Scientific and Technical Information of China (English)

    庞惠勇; 葛恒明; 陈晓芹; 刘小林; 李忠典; 张振宇; 张健

    2011-01-01

    Objective:This study was designed to investigate the effect of drug abuse on human immune function by examining the blood CD4+ CD25 + Foxp3 regulatory T cell expression. Methods: Blood samples were collected in 114 different drug taken route and period people. Flow cytometry was employed to examine the expression of CD4 + CD25 + Foxp3 regulatory T cells. Results: The expression of CD4 + CD25 + Foxp3 regulatory T cells was different among different taken route groups (Oral, 49.07% ± 14.88% > intravenous injection, 34.96% ± 13.41% > mixed routes, 26.72% ± 8.49% ). There were significant differences (P<0. 01) between any of the above two groups. We also examined the effect of drug taken period on the expression of CD4+ CD25 + Foxp3 regulatory T cells. For oral taken people, the expression was much lower in the people with taken period longer than 10 years (37. 14% ± 12.29%) compared with those people with shorter drug taken period ( ≤ 10 years) (51.79% ± 10.44%, P < 0. 01 ). For mixed taken route patients, however, the expression increased from 27.06% ± 8.99% in people with ≤ 10 - year drug taken period to 35.47% ± 11.02% in people with > 10 - year drug taken period( P < 0.01 ). There was no significant difference in the intravenous injection group( P >0.05 ). Conclusion: By examining the blood CD4 + CD25 + Foxp3 regulatory T cell expression in the drug abuse population, it was found that different drug taken routes and periods may induce different extents of injury to the body immune function. Our results provide not only an accurate, reliable monitoring index, but also a new approach to examine the immune function in drug abuse population.%目的:探讨外周血CD4+CD25+Foxp3调节性T细胞与吸毒人员机体免疫的关系.方法:采集114名吸毒人员外周血,根据不同吸毒方式和吸毒年限进行分组,应用流式细胞仪检测外周血中CD4+CD25+Foxp3调节性T细胞表达.结果:不同吸毒

  13. In vivo Regulation of the Allergic Response by the Interleukin 4 Receptor Alpha Chain Immunoreceptor Tyrosine-based Inhibitory Motif

    Science.gov (United States)

    Tachdjian, Raffi; Khatib, Shadi Al; Schwinglshackl, Andreas; Kim, Hong Sook; Chen, Andrew; Blasioli, Julie; Mathias, Clinton; Kim, Hye-Young; Umetsu, Dale T.; Oettgen, Hans C.; Chatila, Talal A.

    2010-01-01

    Background Signaling by IL-4 and IL-13 via the IL-4 receptor alpha chain (IL-4Rα) plays a critical role in the pathology of allergic diseases. The IL-4Rα is endowed with an immunoreceptor tyrosine-based inhibitory motif (ITIM), centered on tyrosine 709 (Y709) in the cytoplasmic domain, that binds a number of regulatory phosphatases. The function of the ITIM in the in vivo regulation of IL-4R signaling remains unknown. Objective To determine the in vivo function of the IL-4Rα ITIM using mice in which the ITIM was inactivated by mutagenesis of the tyrosine Y709 residue into phenylalanine (F709). Methods F709 ITIM mutant mice were derived by knockin mutagenesis. Activation of intracellular signaling cascades by IL-4 and IL-13 was assessed by intracellular staining of phosphorylated signaling intermediates and by gene expression analysis. In vivo responses to allergic sensitization were assessed using models of allergic airway inflammation. Results The F709 mutation increased STAT6 phosphorylation by IL-4 and, disproportionately, by IL-13. This was associated with exaggerated Th2 polarization, enhanced alternative macrophage activation by IL-13, augmented basal and antigen-induced IgE responses and intensified allergen-induced eosinophilic airway inflammation and hyperreactivity. Conclusions These results point to a physiologic negative regulatory role for the Y709 ITIM in signaling via IL-4Rα, especially by IL-13. PMID:20392476

  14. Developmental alterations in the alpha-fetoprotein sugar chain in maternal serum analyzed by lectin affinity electrophoresis.

    Directory of Open Access Journals (Sweden)

    Kawahara N

    1999-06-01

    Full Text Available Our purpose was to investigate developmental alterations of human alpha-fetoprotein (AFP oligosaccharides in maternal serum by lectin affinity electrophoresis and to compare the AFP glycoforms in maternal serum with those in umbilical cord serum and amniotic fluid. AFP glycoforms were separated by affinity electrophoresis with concanavalin A (Con A, lentil lectin (LCA, erythroagglutinating phytohemagglutinin (E-PHA and Allomyrina dichotoma lectin (allo A and detected by sensitive antibody affinity blotting. In maternal serum, increased proportions of Con A-nonreactive AFP (AFP-C1, LCA strongly-reactive AFP (AFP-L3 and E-PHA-reactive AFP (AFP-P4 and AFP-P5 decreased gradually during the early gestational weeks. Allo A-nonreactive AFP (AFP-A1 and asialo-AFP were found only in amniotic fluids during early gestational weeks. The percentages of these glycoforms at full term were almost the same among those body fluids. Since the glycoforms of maternal serum AFP were close to those of umbilical cord serum AFP, lectin-affinity electrophoretic analysis of maternal serum AFP may be useful for evaluating the developmental state of fetus by examining the nature of AFP sugar chain.

  15. Immunology Mechanism of CD4+ CD25 T Regulatory Cells Acting on Effector T Cells

    Institute of Scientific and Technical Information of China (English)

    FENGNing-han; WUHong-fei; WUJun; ZHANGWei; SUIYuan-gen; HEHou-guang; ZHANGChun-lei; ZHENGJun-song

    2004-01-01

    Objective: To detect the inhibiting co-stimulating molecule CTLA4 and cytokines secreted by Treg cells, and explore the immunology mechanism of T regulatory cells acting on effector T cells in co-cultured system(CCS) and separating-cultured system(SCS). Methods: Detecting the percentage of CTLA4 and CD28 expressed on the Treg ceils and effector T ceils, and then adding Treg cells to mixed lymphocyte reaction(MLR) system in CCS and TransWeil Milliceil-PCF SCS, at the same time, adding or not adding anti-IL-10 or anti-TGF.II1 to the reacting systems, examining the inhibitory capacity of Treg ceils exerting on the MLR. Results: Compared with effector T cells, Treg cells expressed higher level CTLA4 and secreted much more IL-10 and TGF-β(P<0.01). The inhibitory capacity of Treg cells co-cultured with effector T ceils is much stronger than that in separating cultured group(P<0.01). Moreover, the inhibiting rate of Treg ceils exerting on effector T ceils through secretin_g IL-10 was more powerful than that through secreting TGF-β1 (P<0.01). Coaclusion: Both ceil-to-ceil contact and cytokines secretion mechanisms are involved in CD4+ CD25+ Treg ceils operating function. However, the former is more important. Intresfingly, we for the first time pointfound that IL-10 plays more powerful roles than TGF-β1 in the cytokines secretion mechanism.

  16. Circulating subsets and CD4(+)CD25(+) regulatory T cell function in chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Sanvito, Lara; Makowska, Anna; Gregson, Norman; Nemni, Raffaello; Hughes, Richard A C

    2009-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory disease of the peripheral nervous system that is probably autoimmune in origin. Different components of the adaptive and innate immunity may be responsible for the aberrant response towards nerve antigens. To investigate this, we examined lymphocyte subsets and regulatory T cell (Treg) function in the blood of CIDP patients, healthy controls (HC) and subjects with non-immune mediated neuropathies (other neuropathies, ON). We used flow cytometry to determine the frequency of monocytes, B cells, natural killer (NK) and NK-T cells, total and activated CD4(+) and CD8(+) T cells, effector memory and central memory CD4(+) and CD8(+) T cells, and CD4(+)CD25(high)Foxp3(+) Tregs. Treg function was studied after polyclonal stimulation and antigen specific stimulation with myelin protein peptides in CIDP and HC. There was an increased frequency of monocytes (p = 0.02) and decreased frequency of NK cells (p = 0.02) in CIDP compared with HC but not ON. There were no significant differences in other populations. Treg function was impaired in CIDP compared to HC (p = 0.02), whilst T cell proliferation to myelin protein peptides before and after depletion of Tregs was not different between patients and controls. This study shows increased circulating monocytes and reduced NK cells in CIDP. Although Treg frequency was not altered, we confirm that Tregs display a defect of suppressive function. Myelin protein peptides were not the target of the altered peripheral regulation of the immune response. The mechanisms of peripheral immune tolerance in CIDP and their relevance to the pathogenesis deserve further exploration.

  17. Rapamycin combined with allogenic immature dendritic cells selectively expands CD4+CD25+Foxp3+ regulatory T cells in rats

    Institute of Scientific and Technical Information of China (English)

    Guo-YingWang; QiZhang; YangYang; Wen-JieChen; WeiLiu; NanJiang; Gui-HuaChen

    2012-01-01

    BACKGROUND: Dendriticcells(DCs)caninitiatetheexpansion of regulatory T cells (Tregs), which play an indispensable role in inducing transplantation tolerance. Some studies have investigated the effect of the immunosuppressant rapamycin (Rapa) on Tregs in vitro. However, the in vivo effect of Rapa combined with immature DCs (iDCs) on Tregs is unknown. This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectivelyexpandtheCD4+CD25+Foxp3+ Tregsinarat model. METHODS: Brown Norway rats were injected intravenously with 2×106 Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days. On day 8, the levels of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry. IL-2, IL-4, TGF-β1, and IFN-γ levels in serum were assessed by ELISA. The experimental animals were divided into four groups: control, Rapa-treated, iDC-treated,andcombination-treated. RESULTS: CD4+CD25+Foxp3+ Tregs comprised 7%-8% of CD4+T cells in control rats. Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen. However, the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone. The levels of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3- T cells in CD4+ T cells did not significantly change in the combined group. The TGF-β1 level in serum from the combined group increased significantly compared with the other groups. CONCLUSIONS: A significantly higher percentage of CD4+CD25+ Foxp3+ Tregs was found in rats treated with allogenic iDCs and a short course of Rapa, along with an increase in the TGF-β1 level in serum. This improved protocol may be a promising therapeutic strategy to increase Tregs, which are beneficial to the induction of peritransplant tolerance.

  18. Prognostic value of CD25 expression on lymphocytes and tumor cells in squamous-cell carcinoma of the head and neck

    NARCIS (Netherlands)

    Loose, David; Signore, Alberto; Bonanno, Elena; Vermeersch, Hubert; Dierckx, Rudi; Deron, Philippe; Van de Wiele, Christophe

    2008-01-01

    CD4(+)CD25(+) T-cells play a central role in initiating and maintaining anticancer immune response. On the other hand, CD25(+) is also expressed on tumor cells, the meaning of which is currently unclear. Therefore, this study was designed to determine the prognostic value of the presence of CD4(+)CD

  19. Analysis of CD4+CD25+ Regulatory T Cells and Foxp3 mRNA in the Peripheral Blood of Patients with Asthma

    Institute of Scientific and Technical Information of China (English)

    XUE Keying; ZHOU Yongming; XIONG Shengdao; XIONG Weining; TANG Tao

    2007-01-01

    The changes of CD4+CD25+ regulatory T cells (CD4+CD25+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible roles of CD4+CD25+ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4+CD25+ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4+CD25+ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups (P<0.05). Although the CD4+CD25+ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them (P>0.05). As compared with persistent group, exacerbation group had lower CD4+CD25+ Treg ratio and Foxp3 mRNA (P<0.05). It was indicated that the decrease of CD4+CD25+Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.

  20. A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in Herlitz junctional epidermolysis bullosa: prenatal exclusion in a fetus at risk.

    Science.gov (United States)

    McGrath, J A; Kivirikko, S; Ciatti, S; Moss, C; Dunnill, G S; Eady, R A; Rodeck, C H; Christiano, A M; Uitto, J

    1995-09-01

    Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chains (alpha 3, beta 3, and gamma 2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the alpha 3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA-->TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks' gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation. PMID:8530087

  1. Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25.

    Science.gov (United States)

    Hannani, Dalil; Vétizou, Marie; Enot, David; Rusakiewicz, Sylvie; Chaput, Nathalie; Klatzmann, David; Desbois, Melanie; Jacquelot, Nicolas; Vimond, Nadège; Chouaib, Salem; Mateus, Christine; Allison, James P; Ribas, Antoni; Wolchok, Jedd D; Yuan, Jianda; Wong, Philip; Postow, Michael; Mackiewicz, Andrzej; Mackiewicz, Jacek; Schadendorff, Dirk; Jaeger, Dirk; Zörnig, Inka; Hassel, Jessica; Korman, Alan J; Bahjat, Keith; Maio, Michele; Calabro, Luana; Teng, Michele Wl; Smyth, Mark J; Eggermont, Alexander; Robert, Caroline; Kroemer, Guido; Zitvogel, Laurence

    2015-02-01

    The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4(+) T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor α (IL-2Rα, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma. PMID:25582080

  2. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production

    OpenAIRE

    Zeiser, Robert; Nguyen, Vu H; Beilhack, Andreas; Buess, Martin; Schulz, Stephan; Baker, Jeanette; Contag, Christopher H.; Negrin, Robert S.

    2006-01-01

    CD4+CD25+ regulatory T (Treg) cells control immunologic tolerance and antitumor immune responses. Therefore, in vivo modification of Treg function by immunosuppressant drugs has broad implications for transplantation biology, autoimmunity, and vaccination strategies. In vivo bioluminescence imaging demonstrated reduced early proliferation of donor-derived luciferase-labeled conventional T cells in animals treated with Treg cells after major histocompatibility complex mismatch bone marrow tran...

  3. Immunosuppressive effects of rat mesenchymal stem cells:involvement of CD4+CD25+regulator y T cells

    Institute of Scientific and Technical Information of China (English)

    Zhou Ye; Yan Wang; Hai-Yang Xie and Shu-Sen Zheng

    2008-01-01

    BACKGROUND: Recent studies show that mesenchymal stem cells (MSCs) have immunomodulatory properties. They suppress the immune response to alloantigen and modify the proliferation of T cells. CD4+CD25+ regulatory T cells have strong immunomodulatory potential. However, little is known about the effects of rat MSCs (rMSCs) on the development of regulatory T cells. METHODS:MSCs were obtained from bone marrow of male Sprague-Dawley rats, and co-cultured with CD3+ T cells from allogeneic spleen cells. The proportion of CD4+CD25+ regulatory  T  cells  was  analyzed  by  lfow  cytometry.  To further conifrm the immunosuppressive activity of rMSCs, we used MTT assay and lfow cytometry of CD3+ T cells to investigate the proliferative responses of CD3+ T cells to mitogenic stimuli. Enzyme-linked immunosorbent assay was performed to detect alterations of the cytokines TNF-α, TGF-β and IL-10. RESULTS:The proliferation of CD3+ T cells decreased when co-cultured with rMSCs, and the degree of inhibition was concentration-dependent. The percentage of CD4+CD25+ regulatory T cells increased when CD3+ T cells were co-cultured with different concentrations of rMSCs. The levels of pro-inlfammatory cytokine (TNF-α) decreased while anti-inlfammatory (TGF-β, IL-10) cytokines increased in mixed lymphocyte reaction. CONCLUSIONS:rMSCs inhibit allogeneic T cell proliferation in mixed cell cultures. This immunosuppressive effect seems  to  be  mediated  by  inducing  the  generation  of CD4+CD25+ regulatory T cells and soluble factors.

  4. 抗人CD25嵌合抗体基因的构建及其瞬时表达研究%Study on construction and transient expression of human-mouse chimeric antibody gene against human CD25

    Institute of Scientific and Technical Information of China (English)

    胡迪超; 张爱华; 潘勇兵; 詹珊珊; 杨晓明

    2011-01-01

    目的:构建抗人CD25嵌合抗体基因并在哺乳动物细胞中进行瞬时表达和初步鉴定.方法:采用RLM-RACE法克隆WuTac抗体可变区和信号肽序列,并利用基因拼接法构建嵌合抗体基因.用脂质体法瞬时转染三种哺乳动物细胞,并使用ELISA、FCM、WB、Dot blot和免疫荧光法进行检测.结果:成功克隆WuTac抗体可变区和信号肽序列,并构建了抗人CD25嵌合抗体表达质粒.瞬时转染结果表明所表达的嵌合抗体保留了亲本抗体WuTac的抗原结合力.结论:成功构建了抗人CD25嵌合抗体基因,为其进一步研究打下基础.%Objective:To construct chimeric antibody gene against human an CD25 angigen,and prelin inarily identify the expressed prod-ucts produced from transiently transfected mammalian cells in order to facilitate the further study of stable expression.Methods:The RLM-RACE was employed to clone variable region genes and leader sequences,and the Overlap PVR method was used to construct the chimeric anti-body gene.After transiently transfected in three mammalian cells with liposome method, the expressed products were determined by ELISA,FCM,W B,Dotblot and immunofluorescence assay.Results:The variable region genes and leader sequences were successfully amplified,and the eukayotic expression plasmids were constructed.The results from transient transfection indicate the expressed products retain the antigen binding capacity of parental antibody WuTac.Conclusion:The successfully constructed chimeric antibody gene against human CD25 lays sound foun-dation for further study.

  5. The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells.

    Science.gov (United States)

    Rawstron, A C; Fenton, J A; Ashcroft, J; English, A; Jones, R A; Richards, S J; Pratt, G; Owen, R; Davies, F E; Child, J A; Jack, A S; Morgan, G

    2000-12-01

    Interleukin-6 (IL-6) is reported to be central to the pathogenesis of myeloma, inducing proliferation and inhibiting apoptosis in neoplastic plasma cells. Therefore, abrogating IL-6 signaling is of therapeutic interest, particularly with the development of humanized anti-IL-6 receptor (IL-6R) antibodies. The use of such antibodies clinically requires an understanding of IL-6R expression on neoplastic cells, particularly in the cycling fraction. IL-6R expression levels were determined on plasma cells from patients with myeloma (n = 93) and with monoclonal gammopathy of undetermined significance (MGUS) or plasmacytoma (n = 66) and compared with the levels found on normal plasma cells (n = 11). In addition, 4-color flow cytometry was used to assess the differential expression by stage of differentiation and cell cycle status of the neoplastic plasma cells. IL-6R alpha chain (CD126) was not detectable in normal plasma cells, but was expressed in approximately 90% of patients with myeloma. In all groups, the expression levels showed a normal distribution. In patients with MGUS or plasmacytoma, neoplastic plasma cells expressed significantly higher levels of CD126 compared with phenotypically normal plasma cells from the same marrow. VLA-5(-) "immature" plasma cells showed the highest levels of CD126 expression, but "mature" VLA-5(+) myeloma plasma cells also overexpressed CD126 when compared with normal subjects. This study demonstrates that CD126 expression is restricted to neoplastic plasma cells, with little or no detectable expression by normal cells. Stromal cells in the bone marrow microenvironment do not induce the overexpression because neoplastic cells express higher levels of CD126 than normal plasma cells from the same bone marrow in individuals with MGUS. (Blood. 2000;96:3880-3886)

  6. The properties of the single chicken MHC classical class II alpha chain ( B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules

    DEFF Research Database (Denmark)

    Salomonsen, Jan; Marston, Denise; Avila, David;

    2003-01-01

    significantly in the peptide-binding alpha(1) domain. The cDNA and genomic DNA sequences from chickens of diverse origins show few alleles, which differ in only four nucleotides and one amino acid. In contrast, significant restriction fragment length polymorphism is detected by Southern blot analysis of genomic...... DNA, suggesting considerable diversity around the gene. Analysis of a large back-cross family indicates that the class II alpha chain locus ( B-LA) is located roughly 5.6 cM from the MHC locus, which encodes the classical class II beta chains. Thus the chicken class II alpha chain gene is like the...

  7. Comparative Study of Regulatory T Cell Function of Human CD25+CD4+ T Cells from Thymocytes, Cord Blood, and Adult Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Wakae Fujimaki

    2008-01-01

    Full Text Available CD25+CD4+ regulatory T cells suppress T cell activation and regulate multiple immune reactions in in vitro and in vivo studies. To define the regulatory function of human CD25+CD4+ T cells at various stages of maturity, we investigated in detail the functional differences of CD25+CD4+ T cells from thymocytes, cord blood (CB, and adult peripheral blood (APB. CB CD25+CD4+ T cells displayed low-FOXP3 protein expression level and had no suppressive activity. In contrast, CD25+CD4+ T cells from thymocytes or APB expressed high expression level of FOXP3 protein associated with significant suppressive activity. Although CB CD25+CD4+ T cells exhibited no suppressive activity, striking suppressive activity was observed following expansion in culture associated with increased FOXP3 expression and a shift from the CD45RA+ to the CD45RA− phenotype. These functional differences in CD25+CD4+ T cells from Thy, CB, and APB hence suggest a pathway of maturation for Treg in the peripheral immune system.

  8. Seasonal influences of winter and summer on CD4+CD25+Treg in SD rats of RA kidney deficiency%冬夏季节肾虚型痹证大鼠CD4+CD25+Treg表达变化

    Institute of Scientific and Technical Information of China (English)

    张淼; 王彤; 陈怀民; 陈彦钦; 邓杨春

    2013-01-01

    目的:以中医学“天人相应”的整体调控思想为指导,以“肾应冬”为切入点,从褪黑素高位调节的角度,通过动物实验探讨肾虚型痹证CD4+CD25+调节性T细胞(Treg)表达的变化.方法:采用胶原诱导的关节炎(CIA)大鼠模型,以冬至、夏至两个时间点,测定各组大鼠血清中CD4+CD25+ Treg/CD4+ Treg变化.结果:与正常组大鼠相比,CIA模型组、手术组及伪手术组CD4+CD25+Treg/CD4+Treg水平均明显降低,并且差异具有统计学意义(P<0.05,P<0.01).说明痹证可导致Treg水平降低.在季节性比较中,冬季正常组、CIA模型组及伪手术组大鼠Treg水平明显低于夏季组,且差异具有统计学意义(P<0.05,P<0.01).结论:Treg水平的改变具有自然节律性,人体冬天的免疫能力低于夏天,正与冬季阳气藏于内的中医理论相一致.%Objective:From the Chinese medicine point of view,man and nature should be in correspondence.Following its overall regulation as guidance and putting‘kidney should be winter'as an entry point,the essay investigates the relationship between RA (a Chinese medicine category) Kidney deficiency CD4+CD25+ Treg and the season changes through animal experiments.Methods:Adopting collagen Ⅱ-induced arthritis,CIA rat model which was the closest to the human RA clinical features,in the Winter Solstice and Summer solstice,the observation on the arthritis index of each rats group and the level change evaluationfor the CD4+ CD25+ Treg/CD4+ Treg.Results:Compared with normal group rat,the CD4+CD25+ Treg/CD4+Treg level of the model of rheumatoid arthritis,CIA group,operation group,and the sham-operation group was significantly decreased and the difference had statistics significance (P<0.05,P<0.01).It proved that RA could lead to the decrease of the treg level.In the season comparison,the treg level of the winter normal group,the model of rheumatoid arthritis,CIA group and the sham operation group was lower than the summer

  9. 肥大细胞体外诱生CD4~+CD25~+Foxp3~+调节性T细胞的作用%Mast cells induce CD4~+CD25~+Foxp3~+ regulatory T cells in vitro

    Institute of Scientific and Technical Information of China (English)

    张维娜; 周巧丹; 雒真龙; 陈忠华; 吴轲; 周鸿敏; 何文涛; 高英; 汪理; 林星光; 方泽民; 蔡兰军

    2009-01-01

    探索小鼠骨髓源性肥大细胞能否在体外诱生CD4~+CD25~+Foxp3~+调节性T细胞.从小鼠股骨获取骨髓细胞,加入完全RPMI 1640培养基(含IL-3和SCF各10 ng/m1)诱导4周.用甲苯胺蓝染色法观察肥大细胞异染颗粒;流式检测CD117和FcεRIα双阳性细胞比例.将肥大细胞与同基因来源的T细胞按不同比例(1,2、1:1、2:1)置于48孔培养板中培养,作为三个实验组;未加肥大细胞的单独T细胞组作对照组.四个组均加入CD3抗体和CD28抗体各2μg/ml,IL-2 1 000U/ml,5 d后流式检测Foxp3表达情况.RT-PCR,免疫组化法检测肥大细胞中TGF-β1的表达.与对照组相比,实验组Foxp3表达均升高(对照组:3.37%±0.40%;实验组为:8.23%±0.80%、10.87%±1.25%、13.63%±0.55%).RT-PCR和免疫组化均检出TGF-β1表达.肥大细胞能在体外诱导T细胞转化为CD4~+CD25~+Foxp3~+调节性T细胞,可能与肥大细胞表达TGF-β1有关.%To detect whether mouse mast cells can induce CD4~+ CD25~+ Foxp3+ regulatory T cells (Treg) in vitro. Bone marrow cells obtained from C57BL/6 (H-2b) mice were cultured with IL-3 (10 ng/ml) and SCF (10 ng/ml) for 4 weeks. The purity of bone marrow mast cells (BMMCs) was tested by flow cytometry. The expression of TGF-β1 in BMMCs was tested by RT-PCR and immunohistochemistry. Then the BMMCs were co-cultured with T cells of C57BL/6 mice at 1 : 2, 1 : 1 and 2 : 1 ratios in the presence of anti-CD3 antibody(2μg/ml), anti-CD28 antibody(2μg/ml) and IL-2 (1 000 U/ml). The percentages of CD4~+ CD25~+ Foxp3+ T cells in the co-cultured system were compared among different groups by flow cytometry on day 5. It was found that the percentages of CD4~+ CD25~+ Foxp3+ cells were significantly higher in the ratio of BMMC/T 2 : 1 group(13.63 ± 0.55%), the 1 : 1 group(10.87% ± 1.25%)and 1 : 2 group(8. 23% ± 0.80%) than in the control group(3.37% ± 0.40%). The expression of TGF-β1 was determined in the mouse BMMCs by RT-PCR and immunohistochemistry. Our find

  10. Restricted TCR-alpha CDR3 diversity disadvantages natural regulatory T cell development in the B6.2.16 beta-chain transgenic mouse.

    Science.gov (United States)

    Singh, Yogesh; Ferreira, Cristina; Chan, Andrew C Y; Dyson, Julian; Garden, Oliver A

    2010-09-15

    To date, analysis of mice expressing TCR-beta transgenes derived from CD4(+) T cell clones has demonstrated equivalent or higher TCR diversity in naturally occurring regulatory CD4(+) T cells (Tregs) versus conventional CD4(+) T cells (Tcons). However, TCR-alpha-chain diversity in these mice may be influenced by the inherent bias toward the CD4(+) lineage in the selected repertoires. We wished to determine whether the choice of TCR-beta-chain influences the relative diversity of the Treg and Tcon repertoires, examining as a model the B6.2.16beta-transgenic mouse, in which the fixed beta-chain is derived from a CD8(+) T cell clone. B6.2.16beta Treg thymocytes showed significantly lower TRAV17 (AV9) CDR3 sequence diversity than both syngeneic Tcon thymocytes, and Treg and Tcon thymocytes from wild-type C57BL/6 (B6) mice. The ratio of single-positive CD4(+)/single-positive CD8(+) thymocytes in B6.2.16beta mice was similar to that in B6, yet both the proportional frequency and absolute number of CD4(+)Foxp3(+) cells was significantly lower in the thymi and peripheral lymph nodes of B6.2.16beta mice. Furthermore, B6 + B6.2.16beta-->B6 mixed bone marrow chimeras revealed that the transgenic beta-chain disadvantaged Treg development in a competitive environment. These data underline the importance of the beta-chain in assessments of Treg alpha-chain diversity and provide further support for the notion that interclonal competition for entry into the Treg lineage is a significant factor in determining the composition of this lineage.

  11. Expansion of CD4(+ CD25(+ and CD25(- T-Bet, GATA-3, Foxp3 and RORγt cells in allergic inflammation, local lung distribution and chemokine gene expression.

    Directory of Open Access Journals (Sweden)

    You Lu

    Full Text Available Allergic asthma is associated with airway eosinophilia, which is regulated by different T-effector cells. T cells express transcription factors T-bet, GATA-3, RORγt and Foxp3, representing Th1, Th2, Th17 and Treg cells respectively. No study has directly determined the relative presence of each of these T cell subsets concomitantly in a model of allergic airway inflammation. In this study we determined the degree of expansion of these T cell subsets, in the lungs of allergen challenged mice. Cell proliferation was determined by incorporation of 5-bromo-2'-deoxyuridine (BrdU together with 7-aminoactnomycin (7-AAD. The immunohistochemical localisation of T cells in the lung microenvironments was also quantified. Local expression of cytokines, chemokines and receptor genes was measured using real-time RT-PCR array analysis in tissue sections isolated by laser microdissection and pressure catapulting technology. Allergen exposure increased the numbers of T-bet(+, GATA-3(+, RORγt(+ and Foxp3(+ cells in CD4(+CD25(+ and CD4(+CD25(- T cells, with the greatest expansion of GATA-3(+ cells. The majority of CD4(+CD25(+ T-bet(+, GATA-3(+, RORγt(+ and Foxp3(+ cells had incorporated BrdU and underwent proliferation during allergen exposure. Allergen exposure led to the accumulation of T-bet(+, GATA-3(+ and Foxp3(+ cells in peribronchial and alveolar tissue, GATA-3(+ and Foxp3(+ cells in perivascular tissue, and RORγt(+ cells in alveolar tissue. A total of 28 cytokines, chemokines and receptor genes were altered more than 3 fold upon allergen exposure, with expression of half of the genes claimed in all three microenvironments. Our study shows that allergen exposure affects all T effector cells in lung, with a dominant of Th2 cells, but with different local cell distribution, probably due to a distinguished local inflammatory milieu.

  12. CD4+CD25+Foxp3+调节性T细胞与自身免疫性疾病%Expression and function of CD4 + CD25 + Foxp3 + in autoimmune diseases

    Institute of Scientific and Technical Information of China (English)

    王露; 张政

    2012-01-01

    自身免疫性疾病系由于机体免疫系统失衡,产生针对自身组织的免疫应答并导致自身组织、器官损害的一类疾病.调节性T淋巴细胞(regulatory T cell,Treg)具有免疫应答低下和免疫抑制特性,在维持机体免疫耐受和免疫应答稳态方面具有非常重要的作用,Treg的异常与多种自身免疫性疾病有关[1].Foxp3特异性表达于CD4+ CD25+ Treg细胞,与其发育、成熟以及抑制功能关系密切.但是目前关于该转录因子的表达调控机制却不清楚.本文拟就CD4+ CD25+ Foxp3 Treg细胞的研究进展及与多种自身免疫性疾病的关系作一综述.%Autoimmune Diseases are disorders caused by immune reactions against self - organs, as results of pathological imbalance of the immune system. New evidences indicates that regulatory T cells (Treg), characterized by immune annergy and immune suppression, have play critical roles in containing immune tolerance, immune response, and homeostasis. The expression of Foxp3, mainly in Treg cells, is thought to be the major factors determining the immune regulative function of Treg. However, F0XP3 regulation is poorly understood. In this article, we reviewed the recent progresses in researches of CD4 + CD25 + Foxp3 + Treg and its role in some autoimmune disease.

  13. Detection and significance of CD4+ CD25+ CD127low/-Treg cells in patients with SLE%系统性红斑狼疮患者外周血CD4+CD25+CD127low/-调节性T细胞的检测及意义

    Institute of Scientific and Technical Information of China (English)

    韦月梅; 邹洪才; 崔俊; 孔建忠; 田安国; 葛建英

    2013-01-01

    Objective To investigate the feasibility of application of CD4+ CD25+ CD127low/- as an Treg cells new marker in patients with systemic lupus erythematosus (SLE). Methods The proportions of CD4+CD25+CD127low-/and CD4+CD25+ FoxP3+Treg cells in peripheral blood of SLE patients(group A) and healthy people(group B) were determined by flow cytometry. The correlation between CD4+ CD25+ CD127low/- Treg cells and CD4+ CD25+ FoxP3+ Treg cells was analyzed. Results The proportions of CD4+CD25+CD127low/- Treg cells and CD4+ CD25+ FoxP3+Treg cells in group A were significantly lower than those in group B [(3. 31 + 0. 82)% and (2. 28 + 0. 47)% vs. (6. 07 + 1. 59)% and (5. 01 + 1. 09)%](P<0. 01). The proportion of CD4+ CD25+ CD127 low/- Treg cells was positively correlated to that of CD4+ CD25+ FoxP3+ T cells in both groups(r=0. 713 and r=0. 709, P<0. 01). Conclusion The surface marker CD4+ CD25+ CD127low/- can be used to identify Treg cells. The decreases of CD4+CD25+CD127low/- Treg cells may play an important role in the pathogenesis of SLE.%目的 探讨用膜表面标志CD4+ CD25+ CD127low/-作为检测调节性T(Treg)细胞标记的可行性,并探讨其在系统性红斑狼疮(SLE)中的临床意义.方法 用流式细胞术检测SLE组及健康对照组外周血CD4+ CD25+ CD127low/-Treg细胞及CD4+ CD25+ FoxP3+ Treg细胞的比例,并分析两组CD4+ CD25+ CD127low/-Treg细胞与CD4+ CD25+ FoxP3+ Treg细胞比例之间的相关性.结果 SLE组外周血CD4+ CD25+ CD127low/-Treg细胞比例为(3.31±0.82)%CD4+ CD25+ FoxP3+ Treg细胞比例为(2.28±0.47)%,均显著低于健康对照组的(6.07±1.59)%和(5.01±1.09)%(P<0.01).SLE组及健康对照组外周血CD4+ CD25+ CD127low/-Treg细胞比例与CD4+ CD25+FoxP3+ Treg细胞比例之间呈显著正相关(r=0.713、r=0.709,P<0.01).结论 膜表面标志CD4+ CD25+ CD127low/-可以用来鉴定Treg细胞;SLE患者外周血CD4+ CD25+ CD127low/-Treg细胞的显著减少可能与SLE的发病有关.

  14. Shen-Qi-Jie-Yu-Fang exerts effects on a rat model of postpartum depression by regulating inflammatory cytokines and CD4+CD25+ regulatory T cells

    Directory of Open Access Journals (Sweden)

    Li JY

    2016-04-01

    Full Text Available Jingya Li,1,* Ruizhen Zhao,1,* Xiaoli Li,1 Wenjun Sun,1 Miao Qu,1 Qisheng Tang,1 Xinke Yang,1 Shujing Zhang2 1Third Affiliated Hospital, 2School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Shen-Qi-Jie-Yu-Fang (SJF is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD. Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim: To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4+CD25+ regulatory T (Treg cells. Materials and methods: Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of Treg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL-1β and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1RI, IL-6Rα, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results: Serum IL-1β in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1β and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1RI and gp130 in PPD rats were consistent with changes in serum IL-1β, and were able to be regulated by SJF and fluoxetine. The levels of Treg cells were negatively correlated with serum IL-1β and IL-6, and were decreased in PPD rats. The levels of Treg cells were increased by SJF and fluoxetine. Conclusion: Dysfunction of proinflammatory cytokines and Tregs in different stages of PPD was attenuated by SJF and fluoxetine through

  15. [Anomaly of the polypeptide and oligosaccharide chains of alpha-2-neuraminoglycoprotein in various types of hereditary angioneurotic edema].

    Science.gov (United States)

    Ollier-Hartmann, M P; Hartmann, L

    1980-05-12

    Using two-dimensional immuno-electrophoresis to study a morphological abnormality of the alpha 2-neuramino-glycoprotein (alpha 2-NGP) we have been able to observe allelic exclusion in patients afflicted by hereditary angioneurotic oedema [1]. With the aid of two-dimensional immuno-affino-electrophoresis, we have been able to show that in some cases, there exists a double abnormality of alpha 2-NGP associating a deficiency in post translating glycosylation with a loss of the inhibitory function of the C1 esterase. PMID:6772326

  16. Vasoactive intestinal peptide-induced expression of cytochrome P450 cholesterol side-chain cleavage and 17 alpha-hydroxylase enzyme activity in hen granulosa cells.

    Science.gov (United States)

    Johnson, A L; Li, Z; Gibney, J A; Malamed, S

    1994-08-01

    Experiments were conducted to determine whether vasoactive intestinal peptide (VIP) can regulate expression of cytochrome P450 side-chain cleavage (P450scc) and P450 17 alpha-hydroxylase (P450 17 alpha-OH) mRNA levels and enzyme activity in granulosa cells from nonhierarchal (6-8-mm) follicles. Initial studies demonstrated that immunoreactive VIP is localized within the theca (but not granulosa) layer of both resting (< 0.5-mm follicles) and 6-8-mm follicles, thus providing a potential paracrine mechanism of action for VIP. While short-term (3 h) incubation of granulosa cells with VIP (0.001-1.0 microM) failed to stimulate progesterone production from 6-8-mm follicle granulosa cells, a 4-h culture period in the presence of VIP resulted in increased cyclic AMP (cAMP) accumulation, and a 24-h culture period resulted in progesterone synthesis and increased P450scc mRNA levels; control levels of each endpoint measurement were not altered within the period observed. By contrast, culture with the growth factor transforming growth factor alpha (TGF alpha) in the presence of VIP (1 microM) prevented increases in P450scc mRNA levels and progesterone production. Similar effects of VIP and TGF alpha in the presence of VIP were demonstrated for P450 17 alpha-OH mRNA levels and enzyme activity. Finally, there was an additive effect of VIP (0.1 microM) plus recombinant human (rh) FSH (100 mIU) on the initiation of progesterone production in cultured 6-8-mm follicle granulosa cells compared to the addition of VIP or rhFSH alone.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. CTLA-4 is Required by CD4+CD25+ Treg to Control CD4+ T Cell Lymphopenia-Induced Proliferation

    OpenAIRE

    Sojka, Dorothy K.; Hughson, Angela; Fowell, Deborah J.

    2009-01-01

    CTLA-4 is constitutively expressed by CD4+CD25+Foxp3+ regulatory T cells (Treg) but its precise role in Treg function is not clear. Although blockade of CTLA-4 interferes with Treg function, studies using CTLA-4 deficient Treg have failed to reveal an essential requirement for CTLA-4 in Treg suppression in vivo. Conditional deletion of CTLA-4 in Foxp3+ T cells disrupts immune homeostasis in vivo but the immune processes disrupted by CTLA-4 deletion have not been determined. We demonstrate tha...

  18. Ribavirin Does Not Impair the Suppressive Activity of Foxp3+CD4+CD25+ Regulatory T Cells

    OpenAIRE

    Lee, Jeewon; CHOI, YOON SEOK; Shin, Eui-Cheol

    2013-01-01

    Ribavirin is an antiviral drug used in combination with pegylated interferon-α (IFN-α) for the treatment of hepatitis C virus (HCV) infection. Recently, ribavirin was reported to inhibit the suppressive activity of regulatory T (Treg) cells. In the present study, we re-evaluated the effect of ribavirin on Foxp3+CD4+CD25+ Treg cells from normal donors. First, we examined the expression of CTLA-4 and CD39, which are known to play a role in the suppressive function of Treg cells. We found that r...

  19. Essential role for interleukin-2 for CD4+CD25+ T regulatory cell development during the neonatal period

    OpenAIRE

    Bayer, Allison L.; Yu, Aixin; Adeegbe, Dennis; Malek, Thomas R.

    2005-01-01

    Although many aspects of CD4+CD25+ T regulatory (Treg) cell development remain largely unknown, signaling through the IL-2R represents one feature for the production of Treg cells. Therefore, the present study was undertaken to further define early developmental steps in the production of Treg cells, including a more precise view on the role of interleukin (IL)-2 in this process. After adoptive transfer of wild-type Treg cells into neonatal IL-2Rβ−/− mice, only a small fraction of donor Treg ...

  20. Distinct roles of CTLA-4 and TGF-b in CD4+ CD25+ regulatory T cell function

    OpenAIRE

    Tang, Qizhi Z; Bluestone, Jeffrey A.

    2004-01-01

    Both CTLA-4 and TGF- have been implicated in suppression by CD4+CD25+ regulatory T cells (Treg). In this study, the relationship between CTLA-4 and TGF- in Treg function was examined. Blocking CTLA-4 on wild-type Treg abrogated their suppressive activity in vitro, whereas neutralizing TGF- had no effect, supporting a TGF--independent role for CTLA-4 in Treg-mediated suppression in vitro. In CTLA-4-deficient mice, Treg development and homeostasis was normal. Moreover, Treg from CTLA-4-deficien...

  1. Reduction of CD4(+)CD25(+) regulatory T-cells in migraine: Is migraine an autoimmune disorder?

    Science.gov (United States)

    Arumugam, Murugesan; Parthasarathy, Varadarajan

    2016-01-15

    Migraine is believed to be a chronic neurological disorder with the exact aetiology being unknown. But, there is a debate on the role of immune dysfunction in migraine pathophysiology. Hence, authors made a debut attempt to explore the link between lymphocyte subset populations and migraine. A significant increase in CD4(+) and decrease in CD8(+) population were observed in migraine patients compared to healthy volunteers. Interestingly, the immunoregulator CD4(+)CD25(+) levels were less in migraine patients compared to the healthy volunteers. The results of the present study indicate that failure of immunoregulation could be implicated in the pathophysiology of migraine.

  2. CD4+ CD25+调节性T细胞及其分子标记物与支气管哮喘

    Institute of Scientific and Technical Information of China (English)

    马祥; 毛辉; 梁宗安

    2009-01-01

    CD4+ CD25+调节性T细胞是一类以免疫抑制和免疫无能为特征的淋巴细胞群,FOXP3是CD4+CD25+调节性T细胞一个特征性的分子标志物,并且对CD4+CD25+调节性T细胞的发育、外周表达和功能维持有着关键性的作用.近年来,多项研究显示CD4+ CD25+调节性T细胞参与并影响了支气管哮喘的发生、发展过程,对调节性T细胞或其相关基因的干预也许会成为支气管哮喘治疗的新方向.

  3. Real-time operating mode with DSSSD detector to search for short correlation ER-alpha chains

    CERN Document Server

    Tsyganov, Yury

    2015-01-01

    Real-time PC based algorithm is developed for DSSSD detector. Complete fusion nuclear reaction natYb+48Ca->217Th is used to test this algorithm at 48Ca beam. Example of successful application of a former algorithm for resistive strip PIPS detector in 249Bk+48Ca nuclear reaction is presented too. Case of alpha-alpha correlations is also under brief consideration.

  4. Single-cell TCRseq: paired recovery of entire T-cell alpha and beta chain transcripts in T-cell receptors from single-cell RNAseq.

    Science.gov (United States)

    Redmond, David; Poran, Asaf; Elemento, Olivier

    2016-01-01

    Accurate characterization of the repertoire of the T-cell receptor (TCR) alpha and beta chains is critical to understanding adaptive immunity. Such characterization has many applications across such fields as vaccine development and response, clone-tracking in cancer, and immunotherapy. Here we present a new methodology called single-cell TCRseq (scTCRseq) for the identification and assembly of full-length rearranged V(D)J T-cell receptor sequences from paired-end single-cell RNA sequencing reads. The method allows accurate identification of the V(D)J rearrangements for each individual T-cell and has the novel ability to recover paired alpha and beta segments. Source code is available at https://github.com/ElementoLab/scTCRseq . PMID:27460926

  5. Lack of Suppressive CD4+CD25+FOXP3+ T Cells in Advanced Stages of Primary Cutaneous T-Cell Lymphoma

    OpenAIRE

    Tiemessen, Machteld M.; Mitchell, Tracey J.; Hendry, Lisa; Whittaker, Sean J; Taams, Leonie S.; John, Susan

    2006-01-01

    Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls. Functional assays demonstrated a dichotomy in Treg function: in four out of 10 patients CD4+CD25+ T cells were incapabl...

  6. TLR5 signaling enhances the proliferation of human allogeneic CD40-activated B cell induced CD4hiCD25+ regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Ping-Lung Chan

    Full Text Available Although diverse functions of different toll-like receptors (TLR on human natural regulatory T cells have been demonstrated recently, the role of TLR-related signals on human induced regulatory T cells remain elusive. Previously our group developed an ex vivo high-efficient system in generating human alloantigen-specific CD4(hiCD25(+ regulatory T cells from naïve CD4(+CD25(- T cells using allogeneic CD40-activated B cells as stimulators. In this study, we investigated the role of TLR5-related signals on the generation and function of these novel CD4(hiCD25(+ regulatory T cells. It was found that induced CD4(hiCD25(+ regulatory T cells expressed an up-regulated level of TLR5 compared to their precursors. The blockade of TLR5 using anti-TLR5 antibodies during the co-culture decreased CD4(hiCD25(+ regulatory T cells proliferation by induction of S phase arrest. The S phase arrest was associated with reduced ERK1/2 phosphorylation. However, TLR5 blockade did not decrease the CTLA-4, GITR and FOXP3 expressions, and the suppressive function of CD4(hiCD25(+ regulatory T cells. In conclusion, we discovered a novel function of TLR5-related signaling in enhancing the proliferation of CD4(hiCD25(+ regulatory T cells by promoting S phase progress but not involved in the suppressive function of human CD40-activated B cell-induced CD4(hiCD25(+ regulatory T cells, suggesting a novel role of TLR5-related signals in the generation of induced regulatory T cells.

  7. Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells

    Institute of Scientific and Technical Information of China (English)

    Qi Cao; Dangsheng Li; Ningli Li; Li Wang; Fang Du; Huiming Sheng; Yan Zhang; Juanjuan Wu; Baihua Shen; Tianwei Shen; Jingwu Zhang

    2007-01-01

    Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Thl immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Thl responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4+CD25+ T cells from the immunized mice. Moreover, CD4+CD25+Foxp3+ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high level of anti-CD25 antibody (about 30 ng/ml,/K0.01 vs controls). Consistent with a role of anti-CD25 response in the down-regulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4+CD25+Foxp3+ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.

  8. 银屑病患者外周血CD4+CD25+调节性T细胞水平的研究

    Institute of Scientific and Technical Information of China (English)

    陈丽芳; 陈小敏; 杨秀丽; 史维平; 秦小卫; 郝树媛

    2007-01-01

    调节性T细胞(regulatory T cell,Treg)是一组具有免疫调节功能的T细胞亚群.对于维持机体内环境的稳定有着重要的作用。根据CD4+CD25+Treg来源的不同将其分为固有CD4+CD25+Treg和适应性CD4+CD25+Treg。固有CD4+CD25+Treg是由胸腺T细胞自然分化发育而来的一个主要Treg亚群,而适应性CD4+CD25+Treg是在特定的免疫环境中,经抗原刺激后成熟的T细胞。我们测定银屑病患者外周血中CD4+CD25+Treg,分析研究其与银屑病的相关性。

  9. Lack of suppressive CD4+CD25+FOXP3+ T cells in advanced stages of primary cutaneous T-cell lymphoma.

    Science.gov (United States)

    Tiemessen, Machteld M; Mitchell, Tracey J; Hendry, Lisa; Whittaker, Sean J; Taams, Leonie S; John, Susan

    2006-10-01

    Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls. Functional assays demonstrated a dichotomy in Treg function: in four out of 10 patients CD4+CD25+ T cells were incapable of suppressing autologous CD4+CD25- T-cell proliferation, whereas suppressive function was intact in the other six patients. Suppressive activity of Tregs inversely correlated with the peripheral blood tumor burden. T-plastin gene expression, used as a Sezary cell marker, confirmed that Sezary cells were heterogeneous for CD25 expression. Mixed lymphocyte reactions demonstrated that CD4+CD25- T cells from patients who lacked functional Tregs were susceptible to suppression by Tregs from healthy controls, and had not become suppressive themselves. Furthermore, we found reduced expression of Foxp3 in the CD4+CD25+ Tregs of these patients relative to the other six CTCL patients and controls. Our findings thus indicate a dysfunction of peripheral Tregs in certain CTCL patients, which correlates with tumor burden.

  10. Induction of CD4+CD25+Foxp3+regulatory T cell response by glatiramer acetate in type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    Guoliang Cui; Yuebo Zhang; Zhenwei Gong; Jingwu Z Zhang; Ying Qin Zang

    2009-01-01

    Glatiramer acetate (GA) is an immunomodulatory peptide drug used to treat multiple sclerosis. Its treatment ef-fect has been expanded to other autoimmune conditions such as uveoretinitis, inflammatory bowel disease, graft re-jection and hepatic fibrosis. Here, we report that GA was effective in altering the clinical course of diabetes in cyclo-phosphamide (CY)-potentiated non-obese diabetic (CY-NOD) mice. Treatment with GA significantly reduced the dia-betic rate in the mice and ameliorated insulitis, which coincided with increased CD4+CD25+Foxp3+T cell response in treated mice. GA treatment led to increased expression of transcription factor Foxp3 and elevated production of interleukin-4 (IL-4) both in vivo and in vitro. It was evident that the effect of GA on up-regulation of Foxp3 was me-diated partially through IL-4. IL-4 was found to maintain Foxp3 expression and regulatory function of CD4+CD25+ regulatory T cells (Tregs). This study provides new evidence that GA has treatment potential for type 1 diabetes through the induction of Tregs and that increased IL-4 production is partially responsible for the enhanced Treg's function in GA treatment.

  11. Protective Effect of CXCR3+CD4+CD25+Foxp3+ Regulatory T Cells in Renal Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Cao Jun

    2015-01-01

    Full Text Available Regulatory T cells (Tregs suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61 + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb to deplete Tregs before renal ischemia. CD4+CD25+Foxp3+ Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN, serum creatinine (Scr levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.

  12. B7-deficient autoreactive T cells are highly susceptible to suppression by CD4(+)CD25(+) regulatory T cells.

    Science.gov (United States)

    May, Kenneth F; Chang, Xing; Zhang, Huiming; Lute, Kenneth D; Zhou, Penghui; Kocak, Ergun; Zheng, Pan; Liu, Yang

    2007-02-01

    CD4(+)CD25(+) regulatory T cells (Tregs) suppress immunity to infections and tumors as well as autoimmunity and graft-vs-host disease. Since Tregs constitutively express CTLA-4 and activated T cells express B7-1 and B7-2, it has been suggested that the interaction between CTLA-4 on Tregs and B7-1/2 on the effector T cells may be required for immune suppression. In this study, we report that autopathogenic T cells from B7-deficient mice cause multiorgan inflammation when adoptively transferred into syngeneic RAG-1-deficient hosts. More importantly, this inflammation is suppressed by adoptive transfer of purified wild-type (WT) CD4(+)CD25(+) T cells. WT Tregs also inhibited lymphoproliferation and acquisition of activation markers by the B7-deficient T cells. An in vitro suppressor assay revealed that WT and B7-deficient T cells are equally susceptible to WT Treg regulation. These results demonstrate that B7-deficient T cells are highly susceptible to immune suppression by WT Tregs and refute the hypothesis that B7-CTLA-4 interaction between effector T cells and Tregs plays an essential role in Treg function.

  13. CD4(+), CD25(+), FOXP3 (+) T Regulatory Cell Levels in Obese, Asthmatic, Asthmatic Obese, and Healthy Children.

    Science.gov (United States)

    Donma, Metin; Karasu, Erkut; Ozdilek, Burcu; Turgut, Burhan; Topcu, Birol; Nalbantoglu, Burcin; Donma, Orkide

    2015-08-01

    The aim of this prospective case control study is to determine CD4(+), CD25(+), and FoxP3(+) T regulatory cells (Tregs) and T helper cells (Ths) in obese, asthmatic, asthmatic obese, and healthy children. Obese (n = 40), asthmatic (n = 40), asthmatic obese (n = 40), and healthy children (n = 40) were included in this study. Blood samples collected from children were marked with CD4, CD25, ve Foxp3 in order to detect Tregs and Ths by flow cytometric method. Statistical analyses were performed. p ≤ 0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0.16 %; p ≤ 0.001), asthmatic (0.25 %; p ≤ 0.01), and asthmatic obese (0.29 %; p ≤ 0.05) groups than control group (0.38 %). Ths were counted higher in asthma group than control (p ≤ 0.01) and obese (p ≤ 0.001) groups. T cell immunity plays important roles in chronic inflammatory diseases such as obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic, and asthmatic obese children might represent a challenge of these cells. PMID:25655390

  14. Protective Effect of CXCR3+CD4+CD25+Foxp3+ Regulatory T Cells in Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Jun, Cao; Qingshu, Li; Ke, Wei; Ping, Li; Jun, Dong; Jie, Luo; Su, Min

    2015-01-01

    Regulatory T cells (Tregs) suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI) is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61) + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb) to deplete Tregs before renal ischemia. CD4+CD25+Foxp3+ Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN), serum creatinine (Scr) levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs. PMID:26273136

  15. Molecular requirements for MHC class II alpha-chain engagement and allelic discrimination by the bacterial superantigen streptococcal pyrogenic exotoxin C.

    Science.gov (United States)

    Kasper, Katherine J; Xi, Wang; Rahman, A K M Nur-Ur; Nooh, Mohammed M; Kotb, Malak; Sundberg, Eric J; Madrenas, Joaquín; McCormick, John K

    2008-09-01

    Superantigens (SAgs) are microbial toxins that bind to both TCR beta-chain variable domains (Vbetas) and MHC class II molecules, resulting in the activation of T cells in a Vbeta-specific manner. It is now well established that different isoforms of MHC II molecules can play a significant role in the immune response to bacterial SAgs. In this work, using directed mutational studies in conjunction with functional analyses, we provide a complete functional map of the low-affinity MHC II alpha-chain binding interface of the SAg streptococcal pyrogenic exotoxin C (SpeC) and identify a functional epitope in the beta-barrel domain that is required for the activation of T cells. Using cell lines that exclusively express individual MHC II isoforms, our studies provide a molecular basis for the selectivity of SpeC-MHC II recognition, and provide one mechanism by how SAgs are capable of distinguishing between different MHC II alleles.

  16. MMP Mediated Degradation of Type IV Collagen Alpha 1 and Alpha 3 Chains Reflects Basement Membrane Remodeling in Experimental and Clinical Fibrosis - Validation of Two Novel Biomarker Assays

    DEFF Research Database (Denmark)

    Sand, Jannie Marie; Larsen, Lise Skakkebæk; Hogaboam, Cory;

    2013-01-01

    Fibrosis is characterized by excessive tissue remodeling resulting from altered expression of various growth factors, cytokines and proteases. We hypothesized that matrix metalloproteinase (MMP) mediated degradation of type IV collagen, a main component of the basement membrane, will release...... peptide fragments (neo-epitopes) into the circulation. Here we present the development of two competitive enzyme-linked immunosorbent assays (ELISAs) for assessing the levels of specific fragments of type IV collagen α1 (C4M12a1) and α3 (C4M12a3) chains in serum as indicators of fibrosis....

  17. 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

  18. An experimental study on inhibiting graft rejection following high-risk penetrating keratoplasty by CD25 siRNA nanocarrier in rats

    Directory of Open Access Journals (Sweden)

    Yun-jie SHI

    2015-06-01

    Full Text Available Objective To investigate the effects of CD25 siRNA nanoparticles against immune rejection and prolongation of corneal graft survival time after high-risk corneal grafting in rats. Methods Orthotopic corneal transplantation was performed in SD rats with alkali burned corneas to mimic high-risk rat models. Donor cornea (Wistar rats was grafted into the right cornea of SD recipients on day 14 after alkali burn. The grafted rats were randomly divided into control group (Group A, EntransterTM-control CD25siRNA instillation treatment (Group B, EntransterTM-CD25siRNA instillation treatment (Group C and EntransterTM-CD25siRNA twice instillation treatment (Group D, first administration at 2-hour post-surgery and second on day 7 post-surgery. The recipient eyes were examined using a slit lamp microscope. Then, the mean survival time and rejection index (RI were calculated. The morphologies of grafts were microscopically examined with HE staining, and TEM. CD25 expression after operation was determined by quantitative RT-PCR and immunohistochemistry. Results The survival curves of transplanted cornea showed that the mean survival time in rats of groups C and D was significantly longer than that in groups A and B (P<0.05. No significant difference was found in survival time between group A and group B, and the same between group C and group D. The grafts in groups A and B showed obvious edema and thickening, with irregular arrangement of collagen fibers and infiltration of a large amount of inflammatory cells. Immunohistochemical results showed that expression of CD25 was found in the corneal epithelium, stroma and endothelium in all rats, and higher CD25 expression was observed in groups A and B. Transmission electron microscopy revealed that the degree of stromal fibroblast apoptosis and necrosis in corneal graft was obviously lower in groups C and D than that of groups A and B, with a significant statistical difference. The expression of CD25 m

  19. A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa.

    Science.gov (United States)

    Kivirikko, S; McGrath, J A; Baudoin, C; Aberdam, D; Ciatti, S; Dunnill, M G; McMillan, J R; Eady, R A; Ortonne, J P; Meneguzzi, G

    1995-05-01

    The inherited mechanobullous disorder, junctional epidermolysis bullosa (JEB), is characterized by extensive blistering and erosions of the skin and mucous membranes. The diagnostic hallmarks of JEB include ultrastructural abnormalities in the hemidesmosomes of the cutaneous basement membrane zone, as well as an absence of staining with antibodies against the anchoring filament protein, laminin 5. Therefore, the three genes encoding alpha 3, beta 3 and gamma 2 chains of laminin 5, known as LAMA3, LAMB3 and LAMC2, are candidate genes for JEB. We have previously demonstrated mutations in the LAMB3 and LAMC2 genes in several families with JEB. We initiated mutation analysis from an affected child by PCR amplification of individual LAMA3 exons, followed by heteroduplex analysis. Nucleotide sequencing of heteroduplexes identified a homozygous nonsense mutation within domain I/II of the alpha 3 chain. These findings provide the first evidence that nonsense mutations within the LAMA3 gene are also involved in the pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5 can result in the JEB phenotype. PMID:7633458

  20. A homozygous nonsense mutation in the {alpha}3 chain gene of laminin 5 (LAMA3) in Herlitz junctional epidermolysis bullosa: Prenatal exclusion in a fetus at risk

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, J.A. [Jefferson Medical College, Philadelphia, PA (United States)]|[St. Thomas Hospital, London (United Kingdom); Ciatti, S.; Christiano, A.M. [Jefferson Medical College, Philadelphia, PA (United States)] [and others

    1995-09-01

    Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chains ({alpha}3, {Beta}3, and {gamma}2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the {alpha}3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA {r_arrow} TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks` gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation. 15 refs., 1 fig.

  1. Physical and linkage mapping of the human and murine genes for the [alpha]1 chain of type IX collagen (COL9A1)

    Energy Technology Data Exchange (ETDEWEB)

    Warman, M.L. (Harvard Medical School, Boston, MA (United States) Children' s Hospital/Harvard Medical School, Boston, MA (United States)); Tiller, G.E.; Polumbo, P.A. (Vanderbilt Univ. Medical Center, Nashville, TN (United States)); Seldin, M.F.; Rochelle, J.M. (Duke Univ. Medical Center, Durham, NC (United States)); Knoll, J.H.M.; Cheng, Sou De (Children' s Hospital/Harvard Medical School, Boston, MA (United States)); Olsen, B.R. (Harvard Medical School, Boston, MA (United States))

    1993-09-01

    The IX collagen, a member of the FACIT family of extracellular matrix proteins, is a heterotrimer composed of three genetically distinct [alpha] chains. The cDNAs for the human and mouse [alpha]1(IX) chains have been cloned. In this paper the authors confirm the mapping of the human COL9A1 gene to chromosome 6q12-q13 by fluorescence in situ hybridization utilizing two genomic clones which also contain short tandem repeat polymorphisms. They also report the characterization of these repeats and their incorporation into the chromosome 6 linkage map. The COL9A1 locus shows no recombination with the marker D6Z1 (Z = 27.61 at [theta] = 0) and identifies the most likely locus order of KRAS1P-[D6Z1-COL9A1]-D6S30. In addition, using an interspecific backcross panel, they have mapped murine Col9a1 to mouse chromosome 1. Together with other comparative mapping results, these data suggest that the pericentric region of human chromosome 6 is homologous to the most proximal segment of mouse chromosome 1. These data may facilitate linkage studies with COL9A1 (or col9a1) as a candidate gene for hereditary chondrodysplasias and osteoarthritis. 35 refs., 2 figs., 2 tabs.

  2. Human mesenchymal stem cells elevate CD4+CD25+CD127low/- regulatory T cells of asthmatic patients via heme oxygenase-1.

    Science.gov (United States)

    Li, Jian-guo; Zhuan-sun, Yong-xun; Wen, Bing; Wu, Hao; Huang, Feng-ting; Ghimire, Hridaya bibhu; Ran, Pi-xin

    2013-09-01

    Up-regulation of CD4+CD25+CD127low/- regulatory T cells (Tregs) is a new target in the treatment of asthma. Human bone marrow mesenchymal stem cells can up-regulate CD4+CD25+CD127low/- regulatory T cells in vitro, meanwhile, heme oxygenase-1 (HO-1) plays an important role in the development and maintenance of CD4+CD25+ regulatory T cells. However the mechanism has not yet been adequately understood. Hence, we wondered what effect of Heme Oxygenase-1 made on regulation of CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells. Peripheral blood mononuclear cells isolated from asthmatic patients and healthy controls were co-cultured with human bone marrow mesenchymal stem cells which were pretreated with Hemin (the revulsive of Heme Oxygenase-1), Protoporphyrin Ⅸ zinc (the inhibitor of Heme Oxygenase-1) and saline. The expression of Heme Oxygenase-1 in MSCs was enhanced by Hemin and inhibited by Protoporphyrin  zinc in vitro. Overexpression of Heme Oxygenase-1 elevated the proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells, meanwhile, inhibition of Heme Oxygenase-1 decreased the proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells as compared with mesenchymal stem cells alone. Taken together, these data demonstrated that Heme Oxygenase-1 contributed to the up-regulation of CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells in asthma.  PMID:23893806

  3. Ⅱ型胶原蛋白对CIA大鼠外周血CD4+CD25+FOXP3+调节性T细胞的影响

    Institute of Scientific and Technical Information of China (English)

    赵海梅; 刘端勇; 程绍民; 左志琴; 辛增平

    2011-01-01

    目的:观察Ⅱ型胶原蛋白对胶原诱导的关节炎(CIA)大鼠外周血CD4+CD25+FOXP3+调节性T 细胞(Treg)的影响.方法:建立Ⅱ型胶原蛋白诱导的大鼠类风湿性关节炎(CIA)模型.采用流式细胞术分别检测正常对照组、模型组、Ⅱ型胶原蛋白治疗组和雷公藤多苷组大鼠外周血CD4+CD25+FOXP3+Treg的水平.结果:与正常对照组比较, 模型组大鼠外周血CD4+T细胞亚群中CD25+FOXP3+Treg的水 平明显下降(P<0. 05或P<0. 01);与模型组比较, Ⅱ型胶原蛋白治疗组大鼠外周血CD25+FOXP3+Treg显著升高(P<0. 05或P<0. 01);而CD25+FOXP3-T细胞和CD25-FOXP3+ T细胞的水平则明显下降(P<0. 05或P<0. 01).结论:Ⅱ型胶原蛋白治疗CIA大鼠的可能途径是升高外周血CD4+CD25+FOXP3+Treg的水平.

  4. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain.

    Science.gov (United States)

    Wang, H Y; Paul, W E; Keegan, A D

    1996-02-01

    IL-4 binds to a cell surface receptor complex that consists of the IL-4 binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (I4R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block Stat6 binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences.

  5. 重组疫苗E.coli LLO/OVA对小鼠CD4+CD25+Treg细胞调节作用的研究%The study for recombinant E.coli LLO/OVA regulating the function of CD4+CD25+Treg cells in mice

    Institute of Scientific and Technical Information of China (English)

    徐曼; 蒋小卫; 米粲

    2009-01-01

    目的:探讨重组E.coli LLO/OVA对小鼠CD4+CD25+Treg细胞的调节作用.方法:E.coli LLO/OVA和E.coli OVA分别免疫小鼠后,磁珠分离脾脏CD11c、CD4+CD25+Treg和CD4+CD25-T细胞,比较两组CD11c细胞对CD4+CD25+Treg细胞分泌IL-10的影响,以及CD4+CD25+Treg细胞抑制CD4+CD25-T细胞增殖的作用;流式细胞术分析荷瘤小鼠OVA特异性CD8+T细胞比率,观察去除CD4+CD25+Treg细胞前后两组黑色素瘤B16-OVA荷瘤小鼠肺转移情况.结果:E.coli LLO/OVA免疫组小鼠脾脏CD4+CD25+Treg细胞产生IL-10水平明显低于E.coli OVA免疫组小鼠(P<0.05),CD4+CD25+Treg细胞对CD4+CD25-T 细胞增殖的抑制作用明显减弱(P<0.05),且OVA特异性CD8+T细胞数量明显增多(P<0.05).在去除CD4+CD25+Treg细胞前后,E.coli LLO/OVA免疫的荷瘤小鼠肺转移结节数无明显减少(P>0.05).结论:重组E.coli LLO/OVA可通过下调小鼠CD4+CD25+Treg细胞数量、抑制其功能而促进机体特异性抗肿瘤免疫.

  6. Frequently Increased but Functionally Impaired CD4+CD25+ Regulatory T Cells in Patients with Oral Lichen Planus.

    Science.gov (United States)

    Zhou, Leilei; Cao, Tianyi; Wang, Yufeng; Yao, Hui; Du, Guanhuan; Chen, Guangjie; Niu, Xiaoyin; Tang, Guoyao

    2016-06-01

    Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucosal disease, and CD4(+)CD25(+) regulatory T cells (Tregs) are considered involved in the pathogenesis of OLP. In this study, to investigate whether there are intrinsic factors that might cause functional changes in Tregs in this disease, we evaluated the frequency of Tregs in peripheral blood and oral lesions and the expression levels of function-related transcription factors, forkhead/winged-helix transcription factor box P3 (FOXP3), transforming growth factor β (TGF-β), interleukin 10 (IL-10), and TGF-β receptors (TβRI and TβRII) mRNAs in Tregs of patients with oral lichen planus (OLP). We also investigated the frequency of pro-inflammatory cytokines (IFN-γ and IL-17A) producing Foxp3(+) regulatory cells. Increased proportions of Tregs were found in OLP patients. The expression of FOXP3 on mRNA and protein level was elevated in the Tregs of OLP. The expression of TGF-β was lower both on the mRNA and serum level, whereas the expression of IL-10 showed no significant difference between the OLP patients and normal controls. The percentages of CD4(+)FOXP3(+)IL-17(+) T cells were significantly higher than that of normal controls, whereas the percentages of CD4(+)FOXP3(+)IFN-γ(+) T cells did not differ significantly. Furthermore, impaired suppressive function of CD4(+)CD25(+) T cells was demonstrated in OLP patients by in vitro proliferation assay. These data indicate that Tregs in OLP are frequently expanded but functionally deficient. This could explain, at least in part, why the increased Tregs in OLP fail to control the pathogenesis and development of this autoimmune disease. PMID:27106476

  7. Deficiency of Mouse CD4+CD25+Foxp3+Regulatory T Cells in Xenogeneic Pig Thymus-Grafted Nude Mice Suffering from Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    Baojun Zhang; Chenming Sun; Yanyan Qu; Aijun Zhang; Jun Liu; Lianjun Zhang; Zeqing Niu; Yong Zhao

    2008-01-01

    Xenogeneic thymus transplantation can efficiently induce specific immune tolerance to donor antigens in athymic recipients.However,many nude mice snffer from autoimmune diseases(AID) for over 10 weeks after xenogeneic thymus transplantation.CD4+CD25+Foxp3+ regulatory T (Treg)cells were recently determined to play a pivotal role in keeping immune tolerance in humans and mice.Thus,we investigated this subpopulation of Treg cells in the periphery of pig thymus-grafted nude mice suffering from AID.Our results showed that the expression of Foxp3, CTLA-4 and GITR on mouse CD4+CD25+T cells and the ratio of CD4+CD25+Foxp3+Treg cells to CD4+T cells were significantly decreased in the periphery of pig thymus-grafted nude mice snfiering from AID,compared with healthy pig or mouse thymus-grafted nude mice.Furthermore,mouse CD4+CD25+T cells in pig thymus-grafted nude mice Sufiering from AID showed more severe deficiency in immunosuppressive function compared with the counterpart in xenogeneic pig or syngeneic thymus-grafted nude mice without AID.Thus,the decreased frequency, altered phenotype and functional deficiency of mouse CD4+CD25+Treg cells in pig thymus-grafted nude mice may contribute to the development of AID in this model.

  8. Studies on the effect and mechanism of CD4+ CD25+ regulatory T calls in Schistosoma japonicum immune evasion%CD4+CD25+调节性T细胞在血吸虫免疫逃避中的作用及机制研究

    Institute of Scientific and Technical Information of China (English)

    唐春莲; 郭思洁; 杨进; 祝青; 刘晓宏

    2014-01-01

    目的 探讨CD4+ CD25+调节性T细胞(Tregs)在日本血吸虫免疫逃避中的作用及其机制.方法 雌性BALB/c小鼠随机分成3组,即正常对照组、感染对照组和抗CD25单克隆抗体(anti-CD25 mAb)组,各感染组每只小鼠均经腹部皮肤感染日本血吸虫尾蚴40条,感染后两周anti-CD25 mAb组每只小鼠经腹腔注射anti-CD25 mAb 300 μg,其它组注射等体积的PBS,感染后5周杀鼠冲虫,计数每只小鼠虫荷.收集脾细胞及培养上清,流式细胞术检测脾淋巴细胞中CD4+ CD25+ Tregs百分比.双抗夹心ELISA法测定脾细胞培养上清中的γ-干扰素(IFN-γ)、IL-4、IL-5、IL-10的含量.结果 Anti-CD25mAb组虫荷(23.17 ±6.94)明显低于感染对照组[(30.17 ±5.85),P=0.047];感染对照组脾淋巴细胞中CD4+ CD25+ Tregs百分比(2.68 ±0.12)%明显高于正常对照组[(1.98±0.33%),P=0.049],而anti-CD25mAb组脾淋巴细胞中CD4+ CD25+ Tregs百分比(1.28±0.30)%明显低于感染对照组(P=0.000);anti-CD25mAb组脾细胞培养上清中IFN-γ的含量(386.87±24.85) pg/mL明显高于感染对照组[(61.32±8.75) pg/mL,P=0.000],其余细胞因子组间无统计学意义.结论 anti-CD25 mAb能部分封闭CD4+ CD25+ Tregs后有利于机体清除日本血吸虫,其机制可能为增强Th1型免疫反应,宿主CD4+ CD25+ Tregs有助于日本血吸虫逃避宿主的免疫攻击.%Objective To explore the effect and mechanism of CD4 + CD25 + Tregs in S.japonicum immune evasion.Methods Female BALB/c mice were randomly divided into normal control group,infected control and anti-CD25 mAb group.Each mouse was infected percutaneously with 40 S.japonicum cercaria.After 2 weeks infection,anti-CD25 mAb group was injected intraperitoneal with 300 μg anti-CD25 mAb each mouse.After 5 weeks infection,all mice were succumbed to measure worm burden.The percent of CD4+ CD25 + Tregs in spleen was measured with flow cytometer.The expression of gamma interferon (IFN-γ),interleukin-4 (IL-4),interleukin-5

  9. The level and significance of CD4 + CD25 + Foxp3 + regulation T cells in leprosy%CD4+CD25+Foxp3+调节性T细胞在麻风病中的水平和意义

    Institute of Scientific and Technical Information of China (English)

    李彩霞; 徐元品; 邹子宏; 周晓鸿

    2013-01-01

    Objective: To detect the expression and significance of CD4+ CD25 + Foxp3 + regulation T cells in leprosy. Methods; The leprosy patients were 51, the cured leprosy people were 26, the ENL were 5, and the normal persons were 56. We used the flow cytometry to test the Tregs in four groups above mentioned. And use the SPSS 19.0 to analysis the results. Results;The percentage of Tregs in leprosy patients, cured people, ENL patients and normal persons were (17.626 ±8.1977)% ,(38.442 ±4.7618)% ,(6. 380 ± 1.5482) % and (9.998 ± 1.7062) %. The Tregs in cured people and leprosy were higher than normal and the Tregs in cured people were higher than leprosy patients, (P < 0.05); The Tregs in ENL were lower than normal; Among leprosy patients(P < 0.05 ) , the Tregs in PB was higher than MB, (P<0.05). Conclusion;Tregs may break the immune tolerance and related to the leprosy.%目的:探讨CD4+ CD25+ Foxp3+调节性T细胞(Treg)在麻风病发病中的作用.方法:采用流式细胞仪检测51例现症麻风患者,5例发生Ⅱ型麻风反应(ENL)的患者,26例治愈麻风患者及56例正常体检者外周血CD4+ CD25+ Foxp3+调节性T细胞(Treg)占CD4+的百分比.结果:现症组、治愈组、Ⅱ型麻风反应(ENL)组及正常对照组外周血Treg的水平分别为:(17.626±8.1977)%、(38.442±4.761 8)%、(6.380±1.548 2)%和(9.998±1.706 2)%.治愈组与现症组麻风患者的Treg高于正常对照组,并且治愈组的Treg比现症组高(P<0.05),ENL组的Treg比正常对照组低(P<0.05);在现症麻风病人中,少菌型患者(PB)及多菌型患者(MB) Treg的百分比分别为:(29.629±7.999 5)%和(15.709±6.4809)%,均高于正常对照组(9.998±1.706 2)% (P <0.05),并且少菌型患者(PB)的Treg高于多菌型患者(MB) (P <0.05).结论:治愈组与现症组麻风患者的Treg均高于正常对照组,发生Ⅱ型麻风反患者(ENL组)的Treg比正常对照组低,Treg可能打破了外周免疫耐受,参与了麻风病的发生发展.

  10. CD4+CD25- T cells that express latency-associated peptide on the surface suppress CD4+CD45RBhigh-induced colitis by a TGF-beta-dependent mechanism.

    Science.gov (United States)

    Oida, Takatoku; Zhang, Xingmin; Goto, Masao; Hachimura, Satoshi; Totsuka, Mamoru; Kaminogawa, Shuichi; Weiner, Howard L

    2003-03-01

    Murine CD4(+)CD25(+) regulatory cells have been reported to express latency-associated peptide (LAP) and TGF-beta on the surface after activation, and exert regulatory function by the membrane-bound TGF-beta in vitro. We have now found that a small population of CD4(+) T cells, both CD25(+) and CD25(-), can be stained with a goat anti-LAP polyclonal Ab without being stimulated. Virtually all these LAP(+) cells are also positive for thrombospondin, which has the ability to convert latent TGF-beta to the active form. In the CD4(+)CD45RB(high)-induced colitis model of SCID mice, regulatory activity was exhibited not only by CD25(+)LAP(+) and CD25(+)LAP(-) cells, but also by CD25(-)LAP(+) cells. CD4(+)CD25(-)LAP(+) T cells were part of the CD45RB(low) cell fraction. CD4(+)CD25(-)LAP(-)CD45RB(low) cells had minimal, if any, regulatory activity in the colitis model. The regulatory function of CD25(-)LAP(+) cells was abrogated in vivo by anti-TGF-beta mAb. These results identify a new TGF-beta-dependent regulatory CD4(+) T cell phenotype that is CD25(-) and LAP(+). PMID:12594277

  11. Graves病患者外周血FOXP3、GITR及CD25基因的表达%Expression of FOXP3, GITR and CD25 genes in peripheral blood of patients with Graves' disease

    Institute of Scientific and Technical Information of China (English)

    王宏伟; 张莹; 陈福琴

    2009-01-01

    目的 研究Graves病(GD)不同阶段患者外周血叉状头/翅膀状螺旋转录因子(FOXP3)、糖皮质激素诱导肿瘤坏死因子受体(GITR)及IL-2受体α链(CD25)基因的表达变化,探讨其在GD发病机制中的作用.方法 收集GD患者90例,按病情分为GD初诊组30例(男13例,女17例);GD缓解组30例(男10例,女20例);GD复发组30例(男11例,女19例).健康查体者30例(男14例,女16例)作为健康对照组.应用实时荧光定量PCR法检测各组外周血单个核细胞中FOXP3、GITR及CIY25 mRNA含量,同时利用电化学发光的方法测定各组血清甲状腺激素水平及甲状腺过氧化酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)的水平.结果 GD各组患者外周血FOXP3mRNA表达均较健康对照组显著降低(P<0.05),GD缓解组FOXP3 mRNA水平较GD初诊组显著升高(P<0.05),复发组FOXP3 mRNA水平虽低于缓解组(P<0.05),但明显高于GD初诊组(P<0.05);GD各组女性患者FOXP3mRNA表达水平显著高于男性患者(P<0.05);Graves初诊及复发组GITR mRNA、CD25mRNA表达水平显著高于对照组(P<0.05).结论 FOXP3、GITR及CD35可能参与了Graves的发生、发展及复发过程.

  12. P38 MAP Kinase Signaling Is Required for the Conversion of CD4+CD25− T Cells into iTreg

    OpenAIRE

    Samuel Huber; Jörg Schrader; Gerhard Fritz; Katrin Presser; Steffen Schmitt; Ari Waisman; Stefan Lüth; Manfred Blessing; Johannes Herkel; Christoph Schramm

    2008-01-01

    CD4+CD25+ regulatory T cells (Treg) are important mediators of immune tolerance. A subset of Treg can be generated in the periphery by TGF-beta dependent conversion of conventional CD4+CD25- T cells into induced Treg (iTreg). In chronic viral infection or malignancy, such induced iTreg, which limit the depletion of aberrant or infected cells, may be of pathogenic relevance. To identify potential targets for therapeutic intervention, we investigated the TGF-beta signaling in Treg. In contrast ...

  13. A phase I study of CD25/regulatory T-cell-depleted donor lymphocyte infusion for relapse after allogeneic stem cell transplantation

    Science.gov (United States)

    Nikiforow, Sarah; Kim, Haesook T.; Daley, Heather; Reynolds, Carol; Jones, Kyle Thomas; Armand, Philippe; Ho, Vincent T.; Alyea, Edwin P.; Cutler, Corey S.; Ritz, Jerome; Antin, Joseph H.; Soiffer, Robert J.; Koreth, John

    2016-01-01

    Donor lymphocyte infusions are used to treat relapse after allogeneic hematopoietic stem cell transplantation, but responses are inadequate. In addition to effector cells, infusions contain CD25+ regulatory T cells (Treg) that may suppress graft-versus-tumor responses. We undertook a phase I study of donor lymphocyte infusions depleted of CD25+ T cells in patients with hematologic malignancies who had relapsed after transplantation. Twenty-one subjects received CD25/Treg-depleted infusions following removal of CD25+ cells using antibody-conjugated magnetic beads. Sixteen subjects received prior cytoreductive therapy. Four were in complete remission at the time of infusion. Two dose levels were administered: 1×107 (n=6) and 3×107 CD3+ cells/kg (n=15). A median 2.3 log-depletion of CD4+CD25+FOXP3+ Treg was achieved. Seven subjects (33%) developed clinically significant graft-versus-host disease by 1 year, including one patient who died. At dose level 1, five subjects had progressive disease and one had stable disease. At dose level 2, nine subjects (60%) achieved or maintained responses (8 complete responses, 1 partial response), including seven with active disease at the time of infusion. A shorter period between relapse and infusion was associated with response at dose level 2 (P=0.016). The 1-year survival rate was 53% among patients treated with dose level 2. Four of eight subjects with acute myeloid leukemia remained in remission at 1 year. When compared to unmodified donor lymphocyte infusions in 14 contemporaneous patients meeting study eligibility, CD25/Treg depletion was associated with a better response rate and improved event-free survival. Circulating naïve and central memory CD4+ T cells increased after CD25/Treg-depleted infusion, but no immunophenotypic signature for response was noted. CD25/Treg-depleted donor infusion appears feasible and capable of inducing graft-versus-tumor responses without excessive graft-versus-host disease. (Clinical

  14. Effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4+ CD25+ Foxp3+ Treg in asthma Balb/c mouse

    OpenAIRE

    Yun, Xiang; SHANG, YUNXIAO; Li, Miao

    2015-01-01

    Background: Bronchial asthma is a chronic airway inflammatory disease that involves T lymphocytes. Methods: In order to explore the effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4+ CD25+ Foxp3+ Treg in asthma Balb/c mouse, we constructed acute asthma model with ovalbumin to observe the mouse behavior change in Balb/c mice. The expression of GATA-3 mRNA and T-bet mRNA was measured by real-time PCR. The proportion of CD4+ CD25+ Foxp3+ Treg/CD4+ was determine...

  15. Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).

    Science.gov (United States)

    Loughlin, J; Irven, C; Hardwick, L J; Butcher, S; Walsh, S; Wordsworth, P; Sykes, B

    1995-09-01

    Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome. However, several candidate genes encoding proteins of the extracellular matrix have been excluded. Using an intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single large pedigree.

  16. Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4{sup +}CD25{sup +} regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Yulan; Purohit, Sharad [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); Department of Pathology, Medical College of Georgia, Georgia Health Sciences University, GA (United States); Chen, Xueqin; Yi, Bing [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); She, Jin-Xiong, E-mail: jshe@georgiahealth.edu [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); Department of Pathology, Medical College of Georgia, Georgia Health Sciences University, GA (United States)

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer This is the first study to provide direct evidence of the role of Stat5b in NOD mice. Black-Right-Pointing-Pointer Over-expression of wild type Stat5b transgene protects NOD mice against diabetes. Black-Right-Pointing-Pointer This protection may be mediated by the up-regulation of CD4{sup +}CD25{sup +} Tregs. -- Abstract: The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4{sup +} T cells and especially CD8{sup +} T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4{sup +} and CD8{sup +} T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-{gamma}, TNF-{alpha} and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4{sup +}CD25{sup +} regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4{sup +}CD25{sup +} regulatory T cells.

  17. Circulating CD4~+CD25~+ and CD8~+CD28~- T regulate cells in multiple myeloma%多发性骨髓瘤患者外周血CD4~+CD25~+和CD8~+CD28~-调节性T细胞研究

    Institute of Scientific and Technical Information of China (English)

    贾丽; 谢晓宝; 邱国强; 钱新瑜; 周民; 肖溶

    2009-01-01

    Objective: The study was designed to evaluate the changes and significance of circulating CD4~+CD25~+ and CD8~+CD28~- regulatory T cells (Tregs) in patients with multiple myeloma (MM).Methods:CD4~+CD25~+ and CD8~+CD28~-Tregs in peripheral blood of 38 patients with MM and of 20 healthy doners were measured by flow cytometry.Serum albumin and β_2-MG in patients with MM were measured using bromocresol green method,transmission turbidimetry respectively.Results:Compared to those of the controls,the proportions of CD4~+CD25~(+/high),CD4~+CD25~(high) CD127~(low) and CD8~+CD28~-Treg cells in newly diagnosed MM patients were elevated.Furthermore,the proportions of CD4~+CD25~(high) and CD4~+CD25~(high)CD127~(low) Tregs in each clinical stage were elevated when compared to those of the controls.The number of the Tregs were increasing with clinical stages and were significantly higher in stage Ⅲ MM than in stageⅠ MM;In stageⅡand Ⅲ MM,there were also elevated proportions of CD8~+CD28~- Tregs,increasing with clinical stages.However,there were no differences when compared between stage Ⅰ MM and the controls;Both the proportions of CD4~+CD25~(+/high) and CD4~+CD25~(high)CD127~(low) Tregs in active MM were not different from stable MM,although all of them were higher than those of controls.The proportion of CD8~+CD28~- Tregs was higher in active MM than in stable MM and controls,but there were no differences when compared between active and stable MM.The proportions of both CD4~+CD25~(high) Tregs and CD4~+CD25~(high)CD127~(low)Tregs had negative correlation with the levels of serum albumin.Conclusion:MM patients have elevated levels of circulating CD4~+CD25~+ and CD8~+CD28~-Tregs,which may be an important mechanism of MM immune evasion,and may be associated with clinical stages,disease progression and prognosis of MM to some extent.%目的:探讨CD4~+CD25~+和CD8~+CD28~-调节性T细胞(Tregs)在多发性骨髓瘤(MM)患者外周血中的变化及意义.方

  18. The Influence of Propofol-Isoflurane Combined Anaesthesia on the T Cell Subpopulations and CD25 Expression%异丙酚-异氟醚复合麻醉对CD25表达及T细胞亚群影响的临床研究

    Institute of Scientific and Technical Information of China (English)

    刘菊英; 田玉科; 骆明恩; 张吉才

    2001-01-01

    The changes of T cell subpopulations (CD+4,CD+8 cell) and CD25+cells and CD25 expression in 40 patients undergoing elective cholecystectomy using either epidural or propofol and isoflurane combined anaesthesia (general anaesthesia) were investigated. Mononuclear cells and erythrocytes were simultaneously isolated before anaesthesia and during operation (60 min after anesthesia induction). Monoclonal antibodies to CD+3,CD+4,CD+ 8 T cells of the T cell subpopulations were identified. CD25 was assessed by immunohistochemistry method. In the patients receiving general anaesthesia,the percentages CD+3,CD+4 CD+8 of the cells were all increased,which were accompanied with a rise of CD25+ cell numbers (P0.05)。CD+3细胞变化两组间具有显著差异(P0.05)。但全麻组麻醉后CD25细胞明显增加(P<0.05)。认为两种麻醉方法对T细胞亚群及淋巴细胞CD25的影响不同。与硬膜外麻醉相比,异丙酚-异氟醚静吸复合全麻使T细胞免疫处于易激活状态。

  19. 离体CD4+CD25+调节性T细胞的扩增和混合淋巴细胞反应研究

    Institute of Scientific and Technical Information of China (English)

    翟海龙

    2011-01-01

    为研究健康人外周血CD4+CD25+调节性T细胞(CD4+CD25+regulatory Tcells,CD4+CD25+Tregs)在协同刺激信号作用下的扩增反应及与CD4+CD25-T细胞混合淋巴细胞反应,采用免疫磁珠法分离CD4+CD25+Tregs和CD4+CD25-T细胞,在抗CD3-mAbs和抗CD28-mAbs的刺激下行CD4+CD25+Tregs培养和CD4+CD25+Tregs+CD4+CD25-T细胞混合淋巴细胞培养72h。然后加入CCK-8溶液孵育1h,用酶标仪检测OD4so值。结果为:CIM+CD25+Tregs组OD。50值极显著性地低于CI)4+CD25-T细胞组(P〈0.01)。CIM+CD25+Tregs与CD4+CD25-T细胞混合组0D450值也极显著性地低于CIM+CD25-T细胞组(P〈0.01)。CD4+CD25+Tregs表现出无反应性特征,还可抑制CD4+CD25-T细胞扩增,因此,CD4+CD25+Tregs不只是很惰性的免疫细胞,而是对保持免疫耐受发挥了积极的调节作用。

  20. Impact of CD4+ CD25+ Regulatory T Cells in Maintenance of Spontaneous Immunotolerance in Mouse Liver Transplantation%CD4+CD25+调节性T细胞在维持小鼠肝脏移植自发性免疫耐受状态中的作用

    Institute of Scientific and Technical Information of China (English)

    姜晓峰; 王学范; 崔哲铭; 朱磊; 郭大伟; 孙文郁; 林琳; 唐裕福; 梁健

    2011-01-01

    目的 探讨CD4+CD25+调节性T细胞在维持小鼠肝脏移植免疫耐受状态中的作用.方法 进行小鼠原位肝脏移植,诱导出移植免疫耐受后,向受体注射抗CD25抗体(PC61)以去除CD4+CD25+T细胞,检测受体内CD4+CD25+T细胞数量及叉状头/翅膀状螺旋转录因子(Foxp3)的表达以确定CD4+CD25+T细胞完全被清除,同时观察受体生存时间.结果 与同种同系小鼠肝脏移植结果 相似,同种异系肝脏移植小鼠的生存时间亦均超过70 d.移植免疫耐受诱导后,PC61不同注射方案均能完全去除受体小鼠肝脏、脾脏及血液中的CD4+CD25+T细胞,且移植肝脏中Foxp3 mRNA的表达也明显降低,表明完全去除了CD4+CD25+调节性T细胞,但肝脏移植动物生存时间并未受到影响.结论 CD4+CD25+调节性T细胞对于小鼠肝脏移植自发性免疫耐受的维持并非必需.%Objective To approach the role of CD4+ CD25+ regulatory T cells in the maintenance of immunotolerance in mouse liver allograft. Methods The mouse orthotopic liver transplantation was performed. After the liver transplantation immunotolerance induction, anti-CD25 monoclonal antibody (PC61) was injected into the recipients with a delayed timing to remove the CD4+ CD25+ T cells. The percentage of CD4+ CD25+ T cells and the expression of fork-head/winged helix transcription factor (Foxp3) in the recipients were examined. Furthermore, the survival time of the recipient was observed. Results C3H/HeJ recipients receiving DBA/2 hepatic allografts survived over 70 d as in the syngeneic liver transplantation (C3H/HeJ recipients receiving C3H/HeJ hepatic grafts).With various protocols of the delayed PC61 treatment, the CD4+ CD25+ T cell was completely disappeared as observed. However, the removal of CD4+ CD25+ regulatory T cells after the induction of transplantation immunotolerance did not affect the survival of hepatic allografts. Conclusion CD4+ CD25+ regulatory T cells are not essential for the

  1. Study of alpha decay chains of superheavy nuclei and magic number beyond Z = 82 and N = 126

    International Nuclear Information System (INIS)

    We study various α-decay chains on the basis of the preformed cluster decay model. Our work targets the superheavy elements, which are expected to show extra stability at shell closure. Our computations identify the following combinations of proton and neutron numbers as the most stable nuclei: Z=112, N=161,163; Z=114, N=171,178,179; and Z=124, N=194. We also investigate the alternative of heavy cluster emissions in the decay chain of 301120, instead of α decay. Our study of cluster radioactivity shows that the half-life for 10Be decay in 289114 is larger, indicating enhanced stability at Z=114, N=175. Similar calculations concerning the emission of 14C and 34Si from 301120 find the more stable combinations Z=114, N=173, and Z=106, N=161, respectively. From the same parent, 301120, the emission of a 49−51Ca cluster yielding a Z=100, N=152 daughter is the most probable. (author)

  2. 小鼠乳腺癌模型中CD4~+CD25~(bright)CCR6~+Treg的检测及其意义%The detection and its significance of CD4~+ CD25~(bright) CCR6~+ Treg regulatory T cells in murine mammary carcinoma model

    Institute of Scientific and Technical Information of China (English)

    徐林; 徐薇; 蒋正刚; 熊思东

    2010-01-01

    为检测CD4~+ CD25~(bright) CCR~(6+) Treg在小鼠乳腺癌实验动物模型中的分布,并探讨其意义.采用FACS检测正常小鼠和4T1荷瘤小鼠中CD4~+ CD25~(bright)Treg的记忆分子CCR6的表达水平,同时检测CD4~+ CD25~(bright)Treg的CCR6~+和CCR6~-两个亚群的Foxp3表达情况;用增殖抑制实验观察了两个亚群分别对CD4~+CD25 T细胞增殖的抑制作用;用FACS检测CD4~+ CD25~(bright)CCR6~+ Treg在正常小鼠和4T1荷瘤小鼠中PBMC、LN和TIL中的分布情况.结果:4T1荷瘤小鼠中CD4~+ CD25~(bright)Treg的记忆分子CCR6的表达水平较正常小鼠增加;CD4~+ CD25~(bright)Treg的CCR6~+和CCR6~-两个亚群均高表达Foxp3,均能在体外有效抑制CD4~+ CD25 T细胞的增殖;与正常对照相比,CD4~+ CD25~(bright)CCR6~+ Treg在4T1荷瘤模型的引流淋巴结中比例明显增加,并在肿瘤局部存在显著的富集.上述结果提示在肿瘤免疫中存在CD4~+ CD25~(bright)CCR6~+ Treg,其具有效应/记忆样表型,并在肿瘤局部有明显的富集,这可能是肿瘤长期免疫逃逸的重要机制.

  3. 哮喘患儿外周血CD4+CD25+调节性T细胞的测定及临床意义%The level of CD4+CD25+regulatory T cells and its clinical significance in children with asthma

    Institute of Scientific and Technical Information of China (English)

    湛洁谊; 卢慧敏; 林穗玲

    2014-01-01

    Objective To explore the proportion change of CD4+CD25+regulatory T cells (Treg) in peripheral blood of children with asthma and to analyze its significance. Methods A total of 150 asthmatic children were divided into three groups according to their clinical features50 subjects in acute asthma attack group, 50 subjects in clinical re-mission of asthma group and 50 subjects in cough variant asthma group,meanwhile, 50 healthy children were enrolled in the control group. The levels of CD4+CD25+Treg in peripheral blood of all children were detected by flow cytometer. Results The CD4+CD25+Treg level in acute attack group were lowest of the four groups (P0.05). Conclusion The CD4+CD25+regulatory T cells may be involved in the pathogenesis of asthma,the level of CD4+CD25+regulatory T cells correlated with the severity of asthma in children.%目的:探讨CD4+CD25+调节性T细胞在哮喘儿童外周血中的比例改变,并探讨其临床意义。方法150例哮喘患儿按临床表现分为急性发作组(50例)、临床缓解期组(50例)和咳嗽变异性哮喘组(50例),另选择50名健康儿童为正常对照组。应用流式细胞仪检测上述各组外周血CD4+CD25+调节性T细胞占CD4+T细胞的百分比。结果急性发作期组患儿外周血CD4+CD25+调节性T细胞水平较缓解组、咳嗽变异性哮喘组及健康对照组明显下降(P0.05)。结论CD4+CD25+调节性T细胞可能参与了哮喘的发生与发展,哮喘的严重程度可能与CD4+CD25+调节性T细胞的水平相关。

  4. 白三烯受体拮抗剂对哮喘气道重塑及Th17细胞/CD4+CD25+调节性T细胞表达的影响%Effects of leukotriene receptor antagonists on airway remodeling and Th17 cells/CD4+CD25+regulatory T cells expresson in asthma

    Institute of Scientific and Technical Information of China (English)

    李丽(综述); 李敏(审校)

    2014-01-01

    支气管哮喘的气道重塑是气道炎症反复作用的结果,白三烯是气道重塑中的重要炎症介质之一。影响气道重塑的因素较多,近年来Th17细胞和CD4+CD25+调节性T细胞(CD4+CD25+treg细胞)在气道重塑中的作用日益受到重视。白三烯受体拮抗剂是治疗哮喘的有效药物,能在一定程度上抑制气道重塑,但其作用机制及对Th17细胞/CD4+CD25+treg细胞表达的影响机制尚不十分清楚。因此,阐明Th17细胞/CD4+CD25+treg细胞平衡在气道重塑中的表达变化、白三烯受体拮抗剂干预气道重塑的具体作用途径和生物效应及对Th17细胞/CD4+CD25+treg细胞表达的影响,将为以后哮喘患儿的预防和治疗提供新的靶点。%The airway remodeling of bronchial asthma is the result of repeated airway inlfammation. Its occurrence is a complex process involving many cytokines, inlfammatory mediators and associated cellular components, of which leukotrienes are important mediators of inlfammation in the airway remodeling. Many factors inlfuence Airway remodeling. In recent years, effects of Th17 cells and CD4+CD25+regulatory T cells (CD4+CD25+treg cells) on airway remodeling is growing in importance. Leukotriene receptor antagonist is an effective drug in the treatment of asthma and can suppress airway remodeling. But the exact mechanisms and its impact on the proportion of Th17 cells/CD4+CD25+treg cells is not yet clear. Therefore, the clariifcation of the changes of Th17 cells/CD4+CD25+treg cells expression in airway remodeling and the speciifc pathways, biological effects, inlfuence of the proportion of Th17 cells/CD4+CD25+treg cells expression after leukotriene receptor antagonist intervene can provide a new target for prevention and the treatment of asthma in the future.

  5. Identification and monitoring of effector and regulatory T cells during experimental arthritis based on differential expression of CD25 and CD134

    NARCIS (Netherlands)

    Nolte-'t Hoen, E.N.M.; Boot, E.P.J.; Wagenaar-Hilbers, J.P.A.; Bilsen, J.H.M. van; Arkesteijn, G.J.A.; Storm, G.; Everse, L.A.; Eden, W. van; Wauben, M.H.M.

    2008-01-01

    Major problems in the analysis of CD4+ effector cell and regulatory T cell (Treg) populations in an activated immune system are caused by the facts that both cell types can express CD25 and that the discriminatory marker forkhead box p3 can only be analyzed in nonviable (permeabilized) cells. Here,

  6. Identification and monitoring of effector and regulatory T cells during experimental arthritis based on differential expression of CD25 and CD134

    NARCIS (Netherlands)

    E.N.M. Nolte-'t Hoen (Esther); E.P.J. Boot (Elmieke); J.P.A. Wagenaar-Hilbers (Josée); J.H.M. van Bilsen (Jolanda); G.J.A. Arkesteijn (Ger); G. Storm; L.A. Everse (Linda); W. van Eden (Willem); M.H.M. Wauben (Marca)

    2008-01-01

    textabstractMajor problems in the analysis of CD4+effector cell and regulatory T cell (Treg) populations in an activated immune system are caused by the facts that both cell types can express CD25 and that the discriminatory marker forkhead box p3 can only be analyzed in nonviable (permeabilized) ce

  7. In vitro effects of mesenchymal stem cells on secreting function of T lymphocytes and CD4~+CD25~+T cells from patients with immune thrombo-cytopenia

    Institute of Scientific and Technical Information of China (English)

    赵霞

    2014-01-01

    Objective To analyze in vitro the effect of mesenchymal stem cells(MSCs)on secreting cytokines by T lymphocytes and ratio of CD4+CD25+T cells from patients with immune thrombocytopenia(ITP).Methods Human bone marrow-derived MSCs were isolated by Ficoll Hypaque and cultured for proliferating to passage cells.Allogeneic T lymphocytes

  8. Diminished frequency and function of CD4(+) CD25(high) regulatory T cells associated with active uveitis in Vogt-Koyanagi-Harada syndrome

    NARCIS (Netherlands)

    Chen, L.; Yang, P.Z.; Zhou, H.Y.; He, H.; Ren, X.R.; Chi, W.; Wang, L.; Kijlstra, A.

    2008-01-01

    PURPOSE. CD4(+)CD25(high) regulatory T (Treg) cells have been shown to be involved in the pathogenesis of autoimmune diseases. Vogt-Koyanagi-Harada (VKH) syndrome is an organ-specific autoimmune disease. This study was designed to phenotypically and functionally characterize peripheral blood CD4(+)C

  9. The relative values of CD8+CD25+Foxp3brigh Treg cells correlate with selected lung function parameters in asthma.

    Science.gov (United States)

    Eusebio, M; Kuna, P; Kraszula, L; Kupczyk, M; Pietruczuk, M

    2015-06-01

    The study aimed to detect CD8(+)CD25(+)FoxP3(brigh) Tregs and investigate their possible association with selected lung function values. CD8(+)CD25(+)FoxP3(brigh) Tregs were detected by flow cytometry in the peripheral blood of 25 patients with severe asthma (SA), 25 patients with mild-to-moderate asthma (MA), and 25 age-matched healthy donors (NC). The percentages of CD8(+)CD25(+)FoxP3(brigh) Tregs of the patients with severe (3.4 ± 4.55), and mild-to-moderate asthma (7.5 ± 8.15), were markedly lower than those of controls (12.1 ± 13.2). The mean forced expiratory volume in 1 s (FEV1) % predicted value in severe asthma subpopulation was significantly lower (67.05 ± 15.98%) when compared with that of mild-to-moderate asthma subgroup (87.71 ± 16.12%). Interestingly, the percentages of CD8(+)CD25(+)FoxP3(brigh) Tregs correlate with mean peak expiratory flow (PEF)% predicted values in severe (r = 0.7, P asthma. In contrast, this parameter was positively correlated with FEV1% predicted values in the severe asthmatics only (r = 0.71, P Tregs and selected lung function parameters, suggesting that this parameter has potential as a marker for inflammation and airflow obstruction. PMID:25921629

  10. Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function

    Directory of Open Access Journals (Sweden)

    Godder Kamar

    2009-10-01

    Full Text Available Abstract Background Foxp3 has been suggested to be a standard marker for murine Tregs whereas its role as marker for human Tregs is controversial. While some reports have shown that human Foxp3+ T cells had no regulatory function others have shown their role in the inhibition of T cell proliferation. Methods T cell activation was performed by means of brayostatin-1/ionomycin (B/I, mixed lymphocyte reaction (MLR, and CD3/CD28 activation. T cell proliferation was performed using BrdU and CFSE staining. Flow cytometry was performed to determine Foxp3 expression, cell proliferation, viabilities and phenotype analyses of T cells. Results Both CD4+ and CD8+ T cells expressed Foxp3 upon activation in vitro. Expression of Foxp3 remained more stable in CD4+CD25+ T cells compared to that in CD8+CD25+ T cells. The CD4+CD25+Foxp3+ T cells expressed CD44 and CD62L, showing their effector and memory phenotypes. Both FoxP3- responder T cells and CD4+FoxP3+ T cells underwent proliferation upon CD3/CD28 activation. Conclusion Expression of Foxp3 does not necessarily convey regulatory function in human CD4+CD25+ T cells. Increased FoxP3 on CD44+ effector and CD44+CD62L+ memory T cells upon stimulation suggest the activation-induced regulation of FoxP3 expression.

  11. Effect of methylprednisolone on CD4 + CD25 + T regulator cells in peripheral blood with asthmatic patients in vitro%甲泼尼龙对哮喘患者外周血CD4+CD25+调节性T细胞影响的体外研究

    Institute of Scientific and Technical Information of China (English)

    鞠云飞; 孙立锋; 胡华; 杨燕; 滕格玲

    2011-01-01

    目的 观察哮喘患者外周血中CD4+ CD25+调节性T细胞(Treg)功能状态及甲泼尼龙对其的影响.方法 清晨取静脉血5 mL,常规分离外周血单个核细胞,分为健康组、哮喘组及1×10-7 mol·L-1甲泼尼龙哮喘干预组,刺激培养48 h,用ELISA法测定IL - 10及TGF - β1的浓度;流式细胞仪检测CD4+ CD25+Treg的比例及细胞内Foxp3表达,用SPSS 17.0进行分析.结果 哮喘组,外周血CD4+ CD25+ Treg细胞比例降低,CD4+ CD25+ Foxp3+ Treg细胞减少,TGF -β1分泌减少,IL - 10分泌有增高趋势,但与健康组比较无统计学意义;甲泼尼龙可以明显增加哮喘急性发作期患者CD4+ CD25+ Treg比例,Foxp3表达明显增强;但未能增加TGF -β1及IL-10的分泌.结论 哮喘患者CD4+ CD25+ Treg功能低下,可能是哮喘发病机制之一;甲泼尼龙可能通过上调CD4+ CD25+ Treg数量,起到控制哮喘急性发作的作用.%Objective To observe the state of CD4+ CD25 + T regulator ( Treg ) cells and the effect of methylprednisolone ( MP) on it in peripheral blood with asthmatic patients. Methods Thirty patients with asthma and 20 healthy controls who visited the Chest Hospital of Shandong Province from Jan, 2010 to Dec, 2010 were included. Five mL fasting blood samples were collected and peripheral blood mononuclear cells ( PBMCs) were isolated using Ficoll - Hypaque density gradient centrifugation. PBMCs were incubated with phytohemagglutinin ( PHA) . The samples were divided into three groups, including healthy control, asthma group, 1 x 10-7 mol · L-1 MP group. After 48 h incubation, supernatant was harvested to determine levels of IL - 10 and TGF - β1 by ELISA. Intracellular 3 - colour flow cytometry were used to assess the expression of Foxp3. All data were analyzed using SPSS 17.0. Results The ratio of CD4+ CD25 + Treg cells and CD4 + CD25 + Foxp3 + Treg cells declined in asthmatic patients compared with healthy control. The secretion of TGF - β1 weaked . The secretion of

  12. Apoptosis induced by low-dose aminophylline in asthmatic peripheral blood CD4+CD25+T regulatory cells%小剂量氨茶碱对支气管哮喘患者外周血CD4+CD25+调节性T细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    梁瑞韵; 伍卫; 黄瑾; 江山平; 张蔚

    2009-01-01

    目的 观察小剂量氨茶碱对分离培养的健康人和支气管哮喘(简称哮喘)患者外周血CD4+CD25+调节性T细胞(T regulatory cells,Treg)凋亡的影响.方法 经密度梯度离心法、尼龙棉柱法、磁珠分离法分离出健康人和哮喘患者外周血CD4+CD25+Treg,分小剂量氨茶碱(1.13 mg/L)、及空白组培养72 h后,用流式细胞仪检测凋亡率变化.结果 ①健康人外周血CD4+CD25+Treg的纯度为77.4%~92.3%,哮喘患者CD4+CD25+Treg的纯度为75.2%~93.8%.②CD4+CD25+Treg占外周血CD4+T细胞的比例在健康组为4.12%~7.98%,在哮喘组为4.51%~8.68%.两者差异无统计学意义.③小剂量氨茶碱均可以诱导健康组及哮喘组外周血CD4+CD25+Treg凋亡率增加(P<0.05).结论 小剂量氨茶碱(1.13 mg/L)可能通过促进CD4+CD25+Treg凋亡来发挥免疫调节作用.

  13. Progress of CD4 + CD25 + regulatory T cells in pathogenesis of idiopathic thrombocytopenic purpura%CD4+CD25+调节性T细胞在特发性血小板减少性紫癜发病机制中的作用

    Institute of Scientific and Technical Information of China (English)

    刘小群

    2011-01-01

    CD4 + CD25 + regulatory T cells(Treg) are thought to be a subgroup of mature CD4 + T cells.Forkhead winged helix transcription factor-3 (Foxp3)is specifically expressed on them and plays a key role in their development and function. CD4 + CD25 + Treg cells can maintain the stabilization of internal environment by two principal pathways to suppress the immunological function: the direct suppression of the target cells by cell-contact and the secretion of suppressor cytokines. At present, it has been considered that decreased number and dysfunction of CD4+ CD25+ Treg cells are closely related to pathogenesis of autoimmune disease. Recent findings show that CD4+ CD25+ Treg cells play an important role in pathogenesis of idiopathic thrombocytopenic purpura.%CD4+ CD25+调节性T细胞(regulatory T cell,Treg)是一种成熟的CD4+T细胞亚群,而叉头翼状螺旋转录因子3(forkhead winged helix transcription factor-3,Foxp3)特异性表达于该细胞上,对其发育和功能起关键作用。CD4+ CD25+ Treg细胞主要通过直接接触和分泌抑制性细胞因子两大途径发挥免疫抑制功能,维持机体内环境的稳定。目前认为其数目减少和功能障碍与自身免疫性疾病的发生密切相关。近年来研究表明CD4+ CD25+ Treg细胞在特发性血小板减少性紫癜的发病中起重要作用。

  14. CD4+CD25+调节性T细胞在不同肝脏肿瘤中的表达及意义%Expression and Significance of CD4+ CD25+ Regulatory T Cells in Different Liver Tumors

    Institute of Scientific and Technical Information of China (English)

    王俊; 罗英; 颜秉菊

    2012-01-01

    目的:研究CD4+CD25+调节性T细胞(Treg)在不同肝脏肿瘤中的分布特点,评价其在肿瘤发生和发展中的作用.方法:根据病理诊断结果将80例肝脏肿瘤分为肝局灶性结节状增生(FNH)组10例、不典型腺瘤样增生(AAH)组10例以及原发性肝癌(HCC)组60例.另选取10例正常肝组织(肝血管瘤边缘肝组织)石蜡包埋标本为对照组.采用双重酶标免疫组化染色的方法测定不同肝脏肿瘤切片中Treg细胞的表达状况.对比分析Treg细胞在FNH、AAH和HCC各组中的表达特点,并进一步分析在HCC组中Treg细胞表达的影响因素.结果:对照组及FNH组中均未发现Treg细胞的表达.AAH组、HCC组中有Treg细胞的表达,且HCC组较AAH组增多(P<0.01).在癌旁组织中已有Treg 细胞浸润,但较肝癌组织中Treg细胞数量少(P<0.01).肝癌组织中不同患者性别、年龄、术前AFP水平的Treg细胞数量差异无统计学意义,而在不同肿瘤大小、肿瘤包膜是否完整及术前HBV-DNA水平是否升高中Treg细胞数量差异有统计学意义(P<0.05或P<0.01).结论:Treg细胞的表达与肿瘤的发生和发展有关,在肿瘤免疫中起负调节作用.%Objective:To investigate the distribution of CD4+CD25+ regulatory T cells(Treg) in different liver tumors, and the role in the process of tumor occurrence and development. Methods: According to the pathological result, 80 patients were divided into focal nodular hyperplasia group (FNH, n=10), atypical adenomatous hyperplasia group (AAH, n=10) and he-patocellular carcinoma group (HCC, n=60). Another 10 cases of normal liver tissue (liver hemangioina edge of the liver) were selected for the control group. The expression of Treg cells in different tumor slices was detected by double ELISA of immuno-histochemical staining. The expression of Treg cells was compared between FNH, AAH and HCC groups. The influencing factors of Treg cells were analyzed between groups in HCC groups. Results

  15. Development of a monoclonal antibody to urinary degradation products from the C-terminal telopeptide alpha 1 chain of type I collagen. Application in an enzyme Immunoassay and comparison to CrossLaps(TM) ELISA

    DEFF Research Database (Denmark)

    C, Fledelius; I, Kolding; P, Quist;

    1997-01-01

    A monoclonal antibody MAbA7 was raised against a synthetic peptide having a sequence (EKAHDGGR) specific for a part of the C-telopeptide alpha 1 chain of type I collagen. MAbA7 was labelled with horseradish peroxide and used in a competitive one-step enzyme-linked immunosorbent assay (ELISA...

  16. QUANTITATION OF DNA TOPOISOMERASE-II-ALPHA MESSENGER-RIBONUCLEIC-ACID LEVELS IN A SMALL-CELL LUNG-CANCER CELL-LINE AND 2 DRUG-RESISTANT SUBLINES USING A POLYMERASE CHAIN REACTION-AIDED TRANSCRIPT TITRATION ASSAY

    NARCIS (Netherlands)

    WITHOFF, S; SMIT, EF; MEERSMA, GJ; van den Berg, Anke; TIMMERBOSSCHA, H; KOK, K; POSTMUS, PE; MULDER, NH; DEVRIES, EGE; BUYS, CHCM

    1994-01-01

    BACKGROUND: We have modified a polymerase chain reaction (PCR)-aided transcript titration assay (1) in order to allow quantitation of low amounts of DNA topoisomerase II alpha mRNA in small RNA samples. EXPERIMENTAL DESIGN: The titration assay was used to quantitate the amount of DNA topoisomerase I

  17. 体外培养扩增CD4+CD25+调节性T细胞的实验观察%Proliferation of CD4+CD25+ regulatory T cells of rat by different cytokines in vitro

    Institute of Scientific and Technical Information of China (English)

    王子函; 朱继业; 李涛; 冷希圣

    2008-01-01

    Objective To evaluate the effects of cytokines on tlle proliferation and function of CD4+CD25+ regulatory T cell(Treg).Mellaotis Tregs were isolated from na(i)ve C57BL/6 mice spleen and lymph nodes.Mature dendritic cells(mDC)were isolated from DBA/2 mice,co-cultured with Tregs,and divided into 4 groups with or without interleukin-2(IL-2),interleukin-4(IL-4),and interleukin-15(IL-15)added into the culture fluid.Fluorescence.activated cell sorting(FACS)was used to detect the Treg proliferation and apoptosis with CFSE and annexin-V staining.The co-cuhure increased Tregs were divided into 5 groups:CFSE labeled naive CIM+ CD25-T cells,self-proliferated Treg,Treg mixedly cultured with IL-2 mDC,and Teff,Treg mixedly cultured with IL-4,mDC,and Teff,and Treg mixedly cultured with IL-15,mDC,and Teff,a control group included Teff co-cultured with mDC.FACS was used 5 d later to evalugte the suppressive function of the Treg Oil the Teff. The expression of Foxp3,indicating the phenotype of Treg was detected.Results FASC showed that the values of precursor frequency(PF)of the Tregs stimulated by IL-2,IL-4,and IL-15 were 31.3%,28.9%,and 34.5%respectively,all significantly higher than that of the control group(14.5% all P<0.05),and the values of proliferation index(PI)of the Tregs stimulated by IL-2,IL-4,and IL-15 were 1.9,1.7,and 1.8 respectively,all significantly higher than that of the control group(1.5,all P<0.05).,The apoptotic rates of the Tregs stimulated by IL-2,IL-4,and IL-15 were 12.8%,11.4%,and 12.7% respectively,all signifieanfly lower tllan that of the control group(28.9%,P<0.05).The Foxp3 expression rate of the Tregs stimulated by IL-2,IL-4,and IL-15was 91.75%.Conclusion IL-2.IL-4.and IL-15 in the in vitro culture of Treg stimulate the Treg proliferation,reduce tlleir apoptosis,and maintain their suppressive function.The proliferated Tregs still maintain their phenotype,highly expressing Foxp3.%目的 观察细胞因子体外培养扩增CD4+CD25+调节性T细

  18. The Detection and Significance of CD4+CD25+CD127lo/-Tregs in Peripheral Blood CD4+T Cells of Healthy and Asthma Patients during Exacerbation and Remission%急性发作期和缓解期哮喘患者外周血CD4+CD25+CD127lo/-Treg的检测和意义

    Institute of Scientific and Technical Information of China (English)

    上官文姬; 沈惠风; 王利民; 叶人诵

    2011-01-01

    目的:通过检测健康人、急性发作期和缓解期哮喘患者外周血CD4+CD25+CD127lo/-Treg细胞的表达水平,探讨该细胞表达水平的变化与哮喘患者病情严重程度的关系.方法:采集急性发作期、缓解期哮喘患者及健康人外周抗凝血,用流式细胞术检测其外周血中CD4+CD25+CD127lo/-Treg细胞占CD4+T细胞的比例.结果:哮喘急性发作组和缓解组患者外周血中CD4+CD25+CD127lo/-Treg细胞占CD4+T细胞的百分比低于健康对照组(P<0.05);哮喘急性发作期组CD4+CD25+CD127lo/-Treg细胞占CD4+T细胞的百分比低于哮喘缓解组(P<0.05).结论:CD4+CD25+ CD127lo/-Treg细胞数量减少可能参与了哮喘的发病过程.%Objective:To investigate the relationship between the expression levels of CD4 + CD25 + CD127lo/-Tregs in peripheral blood of asthma patients during exacerbation or remission. Methods: A total of 2 ml peripheral blood were collected in healthy or asthma patients during exacerbation and remission. The percentage of CD4+ CD25 + CDl27lo/-Tregs in CD4+ T cells by flow cytometry were detected. Results: A significant decrease of the percentage of CD4+ CD25+ CD127lo/- Tregs in CD4+ T cells was observed in exacerbation and remission groups compared with control group (P<0.05). This was also detected in exacerbation group compared with remission group (P<0.05). Conclusions: The CD4+ CD25+ CD127lo/-Tregs play a key role in the pathogenesis of asthma and its decrease,which may lead to immune dysfunction, may be involved in the mechanisms of asthma.

  19. CD4+ CD25+ Foxp3+调节性T细胞在成人过敏性哮喘急性发作期和缓解期外周血中的表达%The Level of CD4+ CD25+ Foxp3+ Tregs in Peripheral Blood of Allergic Asthma Patients with Acute Stage or Stationary Phase

    Institute of Scientific and Technical Information of China (English)

    陈敏; 樊黎; 吴晓立

    2012-01-01

    目的:探讨成人过敏性哮喘急性发作期和缓解期外周血中CD4+ CD25+ Foxp3+ 调节性T 细胞的表达情况及与病情的相关性.方法:收集健康人、过敏性哮喘急性发作期和缓解期患者外周血,流式细胞术测定CD4+ CD25+ Foxp3+ Treg 的比例.结果:CD4+ CD25+ Foxp3+ Treg 细胞在三组间的差异有统计学意义.哮喘缓解期组、哮喘急性期组较健康对照组该细胞比例均明显下降,哮喘急性期组较哮喘缓解期组更低.CD4+ CD25+ Foxp3+ Treg 细胞数量与哮喘病情严重程度呈负相关.结论:CD4+ CD25+ Foxp3+ 调节性T 细胞可能在过敏性哮喘的发病过程中起重要作用,它的降低导致的免疫缺陷可能与哮喘的发生相关.

  20. 哮喘患儿CD4+CD25+T细胞FoxP3表达的意义%Significance of Expression of Intracellular FoxP3 in CD4+CD25+T Cells in Children with Asthma

    Institute of Scientific and Technical Information of China (English)

    陈跃华; 朱华芳; 范婷婷

    2007-01-01

    目的 研究表达FoxP3的CD4+CD25+调节性T细胞在哮喘儿童外周血中的比例改变,探讨其在发病机制中的意义.方法 采用细胞内染色的流式细胞术及定量PCR方法,分别在蛋白质和mRNA水平检测哮喘患儿外周血FoxP3表达,并与健康对照组进行比较.结果 哮喘患儿CD4和CD25双阳性细胞所占比例与健康对照组比较无明显差异,而CD4+CD25high和 CD4+CD25+FoxP3+细胞明显低于对照组(Pa<0.05).FoxP3 mRNA表达水平与蛋白质表达水平变化一致.结论 哮喘患儿CD4+CD25+FoxP3+调节性T细胞明显减少,可能与哮喘的发病机制有关.

  1. Role of CD4+CD25+ regulation cells and expressing of FOXP3 in the pathogenesis of children with asthma%哮喘患儿CD4+CD25+调节性T细胞及FOXP3的表达

    Institute of Scientific and Technical Information of China (English)

    史彧; 褚莉莉; 张兰芳; 赵德育

    2009-01-01

    目的:研究CD4+CD25+调节性T细胞在哮喘儿童外周血中的比例改变,并探讨其临床意义.方法:采用细胞内染色的流式细胞术检测急性发作期哮喘患儿外周血CD4+CD25+Treg及其调控基因FOXP3的表达,并与健康对照组进行比较.结果:急性发作期哮喘患儿外周血CD4和CD25双阳性细胞所占比例与健康对照组无明显差异(P>0.05),而CD4+CD25+FOXP3调节性T细胞在外周血中的比例明显低于健康对照组(P<0.01).结论:哮喘患儿外周血CD4+CD25+FOXP3调节性T细胞在外周血中的比例明显减少,可能与哮喘的发病机制有关.

  2. Changes of CD4+CD25+Regulatory T Cells in Patients with Acute Coronary Syndrome and the Effects of Atorvastatin

    Institute of Scientific and Technical Information of China (English)

    HU Zhenping; LI Dazhu; HU Yingfeng; YANG Keping

    2007-01-01

    The function of CD4+CD25+regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups: group C receiving conventional therapy (n=24), and group C+A receiving conventional therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before and 2 weeks after the treatment) or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to measure the serum levels of cytokines (IL-10, TGF-β1 and IFN-γ) before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly (P<0.01), the in- hibitory ability of Treg on the T lymphocytes proliferation was reduced (P<0.01), IFN-γ, levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvas- tatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were signifi- cantly increased in ACS patients. Serum IFN-γ, was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory ef- fects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restora- tion of immune homeostasis.

  3. Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH genes in multiple human solid tumors: A systematic expression analysis

    Directory of Open Access Journals (Sweden)

    Werbowetski-Ogilvie Tamra

    2008-01-01

    Full Text Available Abstract Background The inter-alpha-trypsin inhibitors (ITI are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by AMBP – and five homologous heavy chains (encoded by ITIH1, ITIH2, ITIH3, ITIH4, and ITIH5, contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis. Methods We systematically investigated differential gene expression of the ITIH gene family, as well as AMBP and the interacting partner TNFAIP6 in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas using cDNA dot blot analysis (Cancer Profiling Array, CPA, semiquantitative RT-PCR and immunohistochemistry. Results We found that ITIH genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, ITIH genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose ITIH2 expression in human breast cancer. Loss of ITIH2 expression in 70% of cases (n = 50, CPA could be confirmed by real-time PCR in an additional set of breast cancers (n = 36. Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p Conclusion Altogether, this is the first systematic analysis on the differential expression of ITIH genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.

  4. 应用iDC从G-CSF动员的外周血中诱导产生CD4+CD25+调节性T细胞%Characteristics of induced CD4+CD25+ regulatory T lymphocytes in G-CSF mobilized peripheral blood by iCD

    Institute of Scientific and Technical Information of China (English)

    苏虹; 王忱诚; 王保龙; 彭美玲

    2012-01-01

    目的 探讨在粒细胞集落刺激因子(G-CSF)动员的外周血单个核细胞(PBMC)中诱导产生CD4+CD25+调节性T细胞(Treg)的可行性及其表型和功能.方法 收集G-CSF动员和未动员的BALB/c ♀鼠的PBMC,采用磁活性标记的细胞分选法 (MACS) 分选BALB/c ♀鼠的CD4+CD25-T细胞和CD4+CD25+T细胞及C57BL/6 ♂鼠的CD11c+未成熟树突细胞(iDC),建立细胞培养体系,经iDC体外诱导G-CSF动员和未动员的CD4+CD25-T细胞转换为CD4+CD25+Treg细胞(iTreg).分别应用流式细胞术、混合淋巴细胞反应技术检测诱导后细胞的CD25、Foxp3的表达水平以及抑制功能,比较G-CSF动员与非动员组间iTreg的表型和抑制功能的差异.结果 iDC诱导G-CSF未动员和动员的组间CD25+分子表达率分别为(76.8±4.1)%和(90.4±5.3)%,差异有统计学意义(P<0.01);两组诱导产生的CD25+T细胞的Foxp3表达水平分别为(64.1±2.7)%和(59.5±3.2)%,差异有统计学意义(P<0.05).iDC诱导G-CSF未动员和动员的外周血产生的iCD4+CD25+Treg均表现出免疫抑制功能,其中动员后诱导生成的iTreg的免疫抑制效应明显增强.结论 应用iDC从G-CSF动员的外周血中诱导产生的iCD4+CD25+Treg具有更强的体外抑制效应,为自身免疫性疾病的治疗提供新的思路和手段.%Objective To explore the feasibility of inducing CD4+ CD25 + regulatory T lymphocytes (Tregs) from mononuclear cells of granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood , and to analyze the phenotype and function of these cells . Methods G-CSF mobilized and un-mobilized peripheral blood mononuclear cells were collected from BALB/c murine. CD4 + CD25 - T cells and CD4 + CD25 + T cells of BALB/c murine, and CDllc+ cells (immature dendritic cell, iDC) of C57BL/6 murine were separated with magnetic activated cell sorting (MACS) respectively. Different cell culture systems were set up to induce CD4+ CD25+ Tregs (iTregs) by iDC from mononuclear cells of G

  5. Proteomic demonstration of the recurrent presence of inter-alpha-inhibitor H4 heavy-chain during aspergillosis induced in an animal model.

    Science.gov (United States)

    Desoubeaux, Guillaume; Jourdan, Marie-Lise; Valera, Lionel; Jardin, Bénédicte; Hem, Sonia; Caille, Agnès; Cormier, Bénédicte; Marchand-Adam, Sylvain; Bailly, Éric; Diot, Patrice; Chandenier, Jacques

    2014-05-01

    Invasive pulmonary aspergillosis remains a matter of great concern in oncology/haematology, intensive care units and organ transplantation departments. Despite the availability of various diagnostic tools with attractive features, new markers of infection are required for better medical care. We therefore looked for potential pulmonary biomarkers of aspergillosis, by carrying out two-dimensional (2D) gel electrophoresis comparing the proteomes of bronchial-alveolar lavage fluids (BALF) from infected rats and from control rats presenting non-specific inflammation, both immunocompromised. A bioinformatic analysis of the 2D-maps revealed significant differences in the abundance of 20 protein spots (ANOVA P-value0.8). One of these proteins, identified by mass spectrometry, was considered of potential interest: inter-alpha-inhibitor H4 heavy-chain (ITIH4), characterised for the first time in this infectious context. Western blotting confirmed its overabundance in all infected BALF, particularly at early stages of murine aspergillosis. Further investigations were carried on rat serum, and confirmed that ITIH4 levels increased during experimental aspergillosis. Preliminary results in human samples strengthened this trend. To our knowledge, this is the first description of the involvement of ITIH4 in aspergillosis. PMID:24360996

  6. Expression of anti-tumor necrosis factor alpha (TNFα) single-chain variable fragment (scFv) in Spirodela punctata plants transformed with Agrobacterium tumefaciens.

    Science.gov (United States)

    Balaji, Parthasarathy; Satheeshkumar, P K; Venkataraman, Krishnan; Vijayalakshmi, M A

    2016-05-01

    Therapeutic antibodies against tumor necrosis factor alpha (TNFα) have been considered effective for some of the autoimmune diseases such as rheumatoid arthritis, Crohn's diseases, and so on. But associated limitations of the current therapeutics in terms of cost, availability, and immunogenicity have necessitated the need for alternative candidates. Single-chain variable fragment (scFv) can negate the limitations tagged with the anti-TNFα therapeutics to a greater extent. In the present study, Spirodela punctata plants were transformed with anti-TNFα through in planta transformation using Agrobacterium tumefaciens strain, EHA105. Instead of cefotaxime, garlic extract (1 mg/mL) was used to remove the agrobacterial cells after cocultivation. To the best of our knowledge, this report shows for the first time the application of plant extracts in transgenic plant development. 95% of the plants survived screening under hygromycin. ScFv cDNA integration in the plant genomic DNA was confirmed at the molecular level by PCR. The transgenic protein expression was followed up to 10 months. Expression of scFv was confirmed by immunodot blot. Protein expression levels of up to 6.3% of total soluble protein were observed. β-Glucuronidase and green fluorescent protein expressions were also detected in the antibiotic resistant plants. The paper shows the generation of transgenic Spirodela punctuata plants through in planta transformation. PMID:25786575

  7. Effect of different doses of rapamycin (RAPA) on Kunming-strain mouse CD4 + CD25 + Treg cells proliferations%不同剂量雷帕霉素对小鼠体内CD4+CD25+Treg细胞的影响

    Institute of Scientific and Technical Information of China (English)

    彭磊磊; 葛圣林; 张成鑫

    2011-01-01

    目的 研究不同剂量雷帕霉素对小鼠体内Treg细胞的影响.方法 将SPF级昆明系小鼠60只随机分为对照组(A)和实验组(B、C、D),B、C、D三组分别灌胃雷帕霉素1、2、3 mg·kg-1,A组每天予以无菌水灌胃,共3周.3周后,无菌条件下心脏采血,EDTA抗凝,分离脾脏,制备单细胞悬液,采用流式细胞仪检测小鼠外周血和脾脏中CD4+CD25+调节性T细胞水平(CD4+CD25+Treg细胞占CD4+ T细胞的百分比).结果 实验组(B、C、D)小鼠外周血和脾细胞中CD4+CD25+Treg细胞水平分别为(9.62±1.43)%、(13.76±1.97)%、(15.41±2.45)%和(12.23±4.56)%、(23.03±6.18)%、(25.17±6.42)%,对照组(A)小鼠外周血和脾细胞中CD4+CD25+Treg细胞水平分别为(3.52±0.65)%和(6.53±3.01)%,无论是在外周血还是脾细胞中,B、C、D组CD4+CD25+Treg细胞水平明显高于A组(P0.05).结论 雷帕霉素能够诱导昆明系小鼠体内CD4+CD25+Treg细胞增殖,其使用剂量可以影响CD4+CD25+Treg细胞的增殖程度.%Aim To investigate how rapamycin (RAPA) at different doses levels induce Kunming-strain mouse CD4 + CD25 + Treg cells proliferations. Methods 60 Kunming-strain mice at the age of 8 weeks were divided into a control group (A) and three experimental groups (B, C,D). The mice in groups B,C and D were fed RAPA 1 ,2 and 3 mg · kg -1 intragastric administration. The mice in group A were given sterile water as the control group. After three weeks, under sterile conditions by collecting the peripheral blood and then seperating the splenocytes (EDTA anticoagulant) ,we were able to generate a single-cell suspension. The level of CD4 + CD25 + Treg cells in the mouse peripheral blood and splenocytes were detected by flow cytometer. (The ratio of CD4 + CD25 + Treg cells to CD4 + CD25 Treg cells). Results The CD4 + CD25 + Treg cells in the mouse peripheral blood and splenocytes of the experimental groups (B, C, D) were (9.62± 1.43)% ,(13.76 ± 1.97)% ,(15.41 ±2.45)% and (12.23 ±4

  8. 高迁移率族蛋白B1对小鼠调节性T细胞与CD4+CD25-T细胞相互作用的影响%Influence of high mobility group box-1 protein on the correlation between regulatory T cells and CD4+CD25-T cells of spleen in mice

    Institute of Scientific and Technical Information of China (English)

    张莹; 姚咏明; 于燕; 吴瑶; 盛志勇

    2008-01-01

    Objective To investigate the influence of high mobility group box-1 protein(HMGB1)on the immunosuppression function of splenic regulatory T cells(Tregs)and its potential regulatory mechanism underlying the effect on CD4+CD25-T cells in mice.nethods CD4+CD25+Tregs isolated from the spleens of male BALB/c mice by magnetic beads were seeded on 96-well(1×105 cells/well)cell culture plates coated with 1 μg/ml anti-CD3 and soluble CD28.After being stimulated with HMGB1 for different time and concentrations,the secretions of IL-2 and IL-10 were analyzed by ELISA.Tregs stimulated for 72 hours were cultured with CD4+CD25-T cells together.The suppressive activity of CD4+CD25+Treg to CD4+CD25-T cells was analyzed by MTT test.IL-2,IL-10,IL-4,and interferon(IFN)-γ in the cell suspensions were determined by ELISA.Resuits After stimulation with HMGB1,the suppressive activity of splenic Tregs in mice were significantly down-regulated at 72 hours,when the proportion of Tregs to CD4+CD25-T cells was 1:1.The secretion of IL-2 of Tregs stimulated by HMGB1 was not markedly changed(P>0.05).while a dose-dependent decrease between IL-10 induction and HMGB1 concentration was obviously(P<0.05).When CD4+CD25-T cells were cultured with stimulated Tregs,comparing with unstimulated-Treg group,levels of IL-2 and IFN-γ were elevated following the increased concentration of HMGB1(P<0.05 or P<0.01).Meanwhile the secretion of IL-4 and IL-10 significantly decreased when cultured with stimulated Tregs(P<0.05).Conclusions These data suggested that HMGB1 stimulation can result in significant down-regulation of immunosuppression of splenic Tregs in mice.HMGB1 might be a potential immunoregnlatory signal that influences the proliferation of effector T cells,secretion of IL-2 and cells-polarization by inhibiting CD4+CD25+Tregs activity.%目的 观察高迁移率族蛋白B1(HMGB1)对调节性T细胞(Treg)与CD4+CD25-T细胞相互作用的影响,并初步探讨其影

  9. 雾化吸入变应原对支气管哮喘外周血CD4+CD25+Foxp3+Treg的影响%Effects of Desensitization of Allergen Nebulization on Blood CD4 + CD25 + Foxp3 + Treg in the Prevention and Treatment of Asthma

    Institute of Scientific and Technical Information of China (English)

    李红华; 赵娟; 张景鸿

    2012-01-01

    Objective To evaluate the effect of allergen nebulization on the ratio of blood CD4 + CD25 + Foxp3 + Treg in asthma. Methods 40 patients with Der. p and Der. f allergy and newly diagnosed uncontrolled moderate persistent bronchial asthma were randomly divided into 2 groups; group A and group B (20 per group). The patients in group B were nebulized with specific allergen twice a week for 6 months. Both groups were treated with salmeterol xinafoate and fluticasone propionate powder. The percentage of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood was determined by flow cytometry. ACT, airway responsiveness and lung function were performed before and after treatment. Results The negative conversion rates of Bronchial Provocation Test in group B were higher than group A significantly. The percentage of CD4 + CD25 + Foxp3 + Treg cells increased in group B when compared with group A(P <0. 05). Conclusion CD4 + CD25 + Foxp3 + T cells played an important immunomudulatory role in immunotherapy of allergen nebulization in treatment of asthma.%目的 探讨CD4+ CD25+ Foxp3+ Treg细胞在哮喘变应原雾化吸入减敏治疗的作用.方法 粉尘螨和屋尘螨点刺阳性的支气管哮喘患者随机分为A组(常规治疗)和B组(变应原吸入减敏),各20例.B组雾化吸入特异性变应原,A组雾化吸入以生理盐水代替,两组给予相同的基础治疗.治疗前、后用流式细胞术(FCM)检测外周血中CD4+CD25+ Foxp3+T细胞占CD4 +T细胞比例;进行哮喘控制评分和肺功能、气道反应性测定.结果 治疗后B组ACT评分高于A组,两组肺功能均有明显增加.B组支气管激发试验转阴率明显高于A组.B组外周血中CD4+ CD25+Foxp3+T细胞占CD4 +T细胞比例较A组明显升高(P<0.05).结论 CD4+ CD25+ Foxp3+T细胞在变应原雾化吸入减敏防治支气管哮喘中发挥免疫调节作用.

  10. Analysis of CD4+CD25+Foxp3+ regulatory T cells in HIV-exposed seronegative persons and HIV-infected persons with different disease progressions.

    Science.gov (United States)

    Li, Lin; Liu, Yongjian; Bao, Zuoyi; Chen, Lili; Wang, Zheng; Li, Tianyi; Li, Hanping; Zhuang, Daomin; Liu, Siyang; Wang, Xiaolin; Li, Jingyun

    2011-02-01

    Regulatory T cells (Tregs) are a subset of T cells that play an important role in the regulation of T-cell function. In a previous study, CD25 was used as a marker of Tregs; however, FoxP3 was recently discovered to be a valuable phenotype of Tregs. In this study, we compared the frequency of Tregs in HIV-1-infected long-term nonprogressors (LTNP), AIDS patients (AP), HIV-exposed seronegative (ES) persons, and healthy controls (HC), by using CD4+CD25+FoxP3+ as a marker of Tregs. The results showed that the frequency of Tregs in AP was significantly higher than in the LTNP, ES, and HC, which suggests that Tregs may play a role in disease progression. Another unique finding in this study is that we found a decrease of Tregs in ES.

  11. Reconstitution of Scid mice with CD4+CD25- T cells leads to rapid colitis: an improved model for pharmacologic testing

    DEFF Research Database (Denmark)

    Kjellev, Stine; Lundsgaard, Dorthe; Poulsen, Steen Seier;

    2006-01-01

    Improved experimental colitis models are needed for evaluation of treatment strategies for IBD. Most current models either lack resemblance to IBD, are complicated to establish, or the colitis occurs slowly and inconsistently. Our aim was to characterize the course of colitis in C.B-17 Scid mice...... was paralleled by increased fecal soluble tumor necrosis factor receptor II content. Cytokines in colonic tissue homogenates exhibited a Th1-like profile. We conclude that adoptive transfer of CD4+CD25- T cells results in colitis resembling IBD with a rapid onset and limited variability between individuals...... reconstituted with syngeneic CD25-depleted CD4+ cells, including the identification of useful biomarkers, and assessment of the similarities to IBD with focus on the relationship between colonic epithelial proliferation and inflammatory parameters. Groups of reconstituted and un-reconstituted mice were...

  12. Neonatal bacillus Calmette-Guerin vaccination inhibits de novo allergic inflammatory response in mice via alteration of CD4+CD25+T-regulatory cells

    Institute of Scientific and Technical Information of China (English)

    Qian LI; Hua-hao SHEN

    2009-01-01

    Aim: The hygiene hypothesis suggests a lack of bacterial infections would favor the development of allergic diseases. My-cobacterium bovis bacille Calmette-Guerin (BCG) infection can inhibit allergen-induced asthma reactions, but the underly-hag mechanism of this infection on the immunological responses is unclear. T-regulatory (Treg) cells are thought to play a role as a crucial immunoregulatory cells that are capable of regulating adaptive immune responses. We conducted this study to investigate whether the protective effect of the BCG vaccination on allergic pulmonary inflammation is associated with the alteration of CD4+CD25+ Treg cells in a murine asthma model and the mechanisms of Treg cells. Methods: Newborn C57BL/6 mice were vaccinated 3 times with BCG on d 0, 7, and 14 and subsequently sensitized and challenged with ovalbumin. Eosinophil infiltration was investigated. The frequencies of spleen CD4+CD25+ Treg cells and the expression of specific transcriptional factor Foxp3 were assayed. The cytotoxic lymphocyte associated antigen (CTLA)-4 expression and cytokine interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) levels were measured. Results: We showed that treatment of mice with BCG inhibited de novo allergic inflammatory response in a mouse model of asthma. BCG treatments are associated with the increase of CD4+CD25+ Treg cells and Foxp3 expression, accompanied by an increased CTLA-4 expression and cytokine IL-10 and TGF-β levels (P<0.05). Conclusion: Neonatal BCG vaccinations ameliorate de novo local eosinophilic inflammation induced by allergen and in-crease the numbers of CD4+CD25+ Treg cells and Foxp3 expression. The cell-cell contact inhibition and regulatory cytokine production may be involved in the regulatory mechanism.

  13. The ex vivo Microenviroments in MLTC of Poorly Immunogenic Tumor Cells Facilitate Polarization of CD4+CD25+ Regulatory T Cells

    Institute of Scientific and Technical Information of China (English)

    Le Zhou; Hongyan Wang; Juxiang Xiao; Lusheng Si; Yili Wang

    2006-01-01

    CD4+CD25+ regulatory T (TR) cells play an important role in maintaining a balanced peripheral immune system.Recent studies have shown that TR cells may also play a key role in suppressing anti-tumor immune response. In order to investigate the tumor immune microenvironment and its influence on TR polarization, poorly immunogenic tumor cell line D5 (C57BL/6, H-2b), immunogenic tumor cell lines FBL3 (C57BL/6, H-2b) and H22 BALB/c, H-2d) were used to establish the syngeneic/allogeneic, poorly immunogenic/immunogenic mixed lymphocytes-tumor cell culture (MLTC). Our results revealed that the proportion of CD4+CD25+ T cells in MLTC of syngeneic primed splenocytes stimulated with D5 tumor cells was higher than that with H22 cells (0.43% vs 0.044%, and the similar results appeared in allogeneic splenocytes stimulated with D5 tumor cells (0.39% vs 0.04%).The splenocytes stimulated with supernatant from syngeneic MLTC of D5 tumor cells demonstrated higher proportion of CD4+CD25+ cells than that from allogeneic MLTC of D5 tumor cells, and the splenocytes stimulated with supernatant from syngeneic or allogeneic MLTC of H22 tumor cells generated lower proportion of CD4+CD25+ T cells than that of D5 tumor cells. The TGF-β1 and Th2-oriented cytokines (IL-4 and IL-10) were dominated in supernatants of syngeneic MLTC of poorly immunogenic tumor cells. Our results provided useful information for studying the mechanisms underlying tumor immune surveillance as well as for the tumor immunotherapy.

  14. Percentage of CD4+, CD8+, and CD25+ T lymphocytes in peripheral blood of pigs in the course of experimental burns and necrectomy

    Directory of Open Access Journals (Sweden)

    Aleksiewicz Roman

    2015-09-01

    Full Text Available The aim of the study was the evaluation of changes in the percentage profile of CD4+, CD8+, and CD25+ T lymphocytes, and their predictive value with respect to the course of experimental skin burns and early necrectomy in pigs. Thirty Large White Landrace pigs of both genders, weighing 50 kg (±2 kg, were used. Burns to their skin were performed with the use of a computer-controlled heating plate, applied to the animal’s body and heated to 2000°C, using 2.5 kg pressure for 10 s. It produced a burn of 30% (±2% of body surface with a range of damage between II b° and III°. In animals of each experimental group fascial necrectomy was performed, according to the testing module. Blood from experimental and non-treated control animals was collected from the external jugular vein before the beginning of the experiment (hour 0 and at 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 h of the experiment. An immune response profile was evaluated using flow cytometry analysis of the level and expression dynamics of CD4+, CD8+, and CD25+ particles on the surface of T lymphocytes. The study demonstrated that experimentally-induced burns in pigs caused cell-mediated immune response reflected in the changes in the percentage of CD4+, CD8+, and CD25+ T lymphocytes, and that early necrectomy in burnt pigs acted in a protective manner for the organism, based on the immunological index values. The study also proved that the dynamics of cell-mediated immunological response intensification determined on the basis of the percentage of CD4+, CD8+, and CD25+ T lymphocytes is conditioned by the size of the burnt surface and the time of necrectomy procedure.

  15. CD4+CD25+ Regulatory T Cells Inhibit Natural Killer Cell Hepatocytotoxicity of Hepatitis B Virus Transgenic Mice via Membrane-Bound TGF-β and OX40.

    Science.gov (United States)

    Chen, Yongyan; Sun, Rui; Wu, Xunyao; Cheng, Min; Wei, Haiming; Tian, Zhigang

    2016-01-01

    CD4+CD25+ regulatory T cells (Tregs) are involved in the regulation of physiological and pathological hepatic immune responses, but the roles are not well explored in natural killer (NK) cell-mediated liver diseases. In this study, using the NK cell-mediated oversensitive liver injury model of hepatitis B virus transgenic (HBs-Tg) mice triggered by a low dose of concanavalin A, it was observed that an increased number of CD4+CD25+Foxp3+ Tregs were accumulated in the liver, along with the recovery of liver injury. Adoptive transfer of hepatic Tregs from HBs-Tg mice but not wild B6 mice could significantly attenuate the oversensitive liver injury via inhibiting liver accumulation and decreasing NK cell group 2D-mediated activation of NK cells in the recipient HBs-Tg mice. Furthermore, upregulated expression of membrane-bound TGF-β (mTGF-β) and OX40 on hepatic Tregs were demonstrated to account for inhibiting the NK cell-mediated hepatic injury in HBs-Tg mice through cell-cell contact, confirmed by antibody blockade and cell Transwell experiments in vivo and in vitro. Our findings for the first time indicated that CD4+CD25+ Tregs directly suppressed NK cell-mediated hepatocytotoxicity through mTGF-β and OX40/OX40L interaction in a cell-cell contact manner in HBV-associated liver disease. PMID:26067079

  16. Serum 25-hydroxyvitamin D and CD4+CD25(+high) FoxP3+ Regulatory T cell as Predictors of Severity of Bronchial Asthma in Children.

    Science.gov (United States)

    Ismail, Ahlam M; Aly, Sanaa S; Fayed, Hanan M; Ahmed, Samar S

    2015-01-01

    Bronchial asthma (BA) is one of the common chronic diseases of childhood. Vitamin D deficiency has been associated with BA. Suppressor regulatory T cells (Treg) are important for the induction, maintenance of immunological tolerance to allergens. This study assessed serum 25-hydroxyvitamin D (vitamin D) and the percentages of CD4+CD25+(high) Foxp3+ Treg, in peripheral blood, as predictors of asthma severity and level of clinical control. The study enrolled 72 children divided equally between asthmatic children (AC) and age and sex matched controls. Diagnostic criteria and level of asthma severity followed the Global Initiative for Asthma guidelines. Serum vitamin D was determined by an immunoassay and the percentages of CD4+CD25+ig Foxp3+ Treg by flow cytometry. Serum vitamin D level and percentage of CD4+CD25+(high) Treg were lower in AC compared to controls (P asthma compared to mild and moderate forms (P = 0.008) and in uncontrolled attacks compared to partially or completely controlled children. No difference in percentage of Treg in relation to asthma severity and clinical control was observed. Since AC has decreased serum vitamin D with inverse relationship between its levels and asthma severity, we conclude that it can be used to predict severity of asthma. PMID:26415368

  17. Impaired NK cells' activity and increased numbers of CD4 + CD25+ regulatory T cells in multidrug-resistant Mycobacterium tuberculosis patients.

    Science.gov (United States)

    Fan, Renhua; Xiang, Yangen; Yang, Li; Liu, Yanke; Chen, Pingsheng; Wang, Lei; Feng, Wenjun; Yin, Ke; Fu, Manjiao; Xu, Yixin; Wu, Jialin

    2016-05-01

    Multidrug-resistant tuberculosis (MDR-TB) often causes persistent infection and chemotherapy failure, which brings heavy burden of society and family. Many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. The presence of regulatory T cells (Tregs) is thought to be an important mechanism that TB successfully evades the immune system. Tregs play a central role in the prevention of autoimmunity and in the control of immune responses. The role of Tregs in MDR-TB infection and persistence is inadequately documented. The current study was designed to determine whether CD4 + CD25+ regulatory T cells may modulate innate immunity (such as NK cells) against human tuberculosis. Our results indicated that the numbers of CD4 + CD25+ Treg cells increased in MDR-TB patients' blood, and the cytokine production of IL-10 increased from MDR-patients compared with healthy subjects, along with the lower activity and low CD69 expression of NK cells in patients. These results suggested that immunity to MDR-TB patients induced circulating CD4 + CD25+ T regulatory cells expansion, which may be related to the persistence of Mycobacterium tuberculosis (M. tb) infection, and to the balance between effectors immune responses and suppression immune responses. PMID:27156613

  18. Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4+ CD25+ regulatory T cells population

    Science.gov (United States)

    Zheng, Quan-you; Liang, Shen-ju; Li, Gui-qing; Lv, Yan-bo; Li, You; Tang, Ming; Zhang, Kun; Xu, Gui-lian; Zhang, Ke-qin

    2016-01-01

    Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3−/−) as skin graft donors or recipients. Compared with C3+/+ B6 allografts, C3−/− B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2bm12 B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3+/+ allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3−/− allografts. Moreover, C3−/− allografts caused attenuated Th1/Th17 responses, but increased CD4+CD25+Foxp3+ regulatory T (Treg) cell expression markedly in local intragraft and H-2bm12 recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4+ CD25+ Treg cell population expansion and attenuated Th1/Th17 response. PMID:27641978

  19. Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population.

    Science.gov (United States)

    Zheng, Quan-You; Liang, Shen-Ju; Li, Gui-Qing; Lv, Yan-Bo; Li, You; Tang, Ming; Zhang, Kun; Xu, Gui-Lian; Zhang, Ke-Qin

    2016-01-01

    Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3(-/-)) as skin graft donors or recipients. Compared with C3(+/+) B6 allografts, C3(-/-) B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2(bm12) B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3(+/+) allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3(-/-) allografts. Moreover, C3(-/-) allografts caused attenuated Th1/Th17 responses, but increased CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell expression markedly in local intragraft and H-2(bm12) recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4(+) CD25(+) Treg cell population expansion and attenuated Th1/Th17 response. PMID:27641978

  20. 安子合剂对ACA阳性先兆流产患者CD4+CD25+FOXP3+Treg细胞免疫调节的影响%TheEffect of Anzi Mixture on Immune Regulation of CD4+CD25+FOXP3+Treg Cells in ACA-positive Patients with Threatened Abortion

    Institute of Scientific and Technical Information of China (English)

    朱姝; 陆启滨

    2012-01-01

    目的:观察安子合剂对ACA阳性先兆流产患者CD4+ CD25+ FOXP3+ Treg细胞免疫调节的影响.方法:选取ACA阳性先兆流产患者为治疗组(27例),给服中药安子合剂,125ml,2次/日,连服4周;选取正常孕妇为对照组(15例).检测患者治疗前后及正常孕妇外周血CD4+ CD25+ FOXP3+ Treg细胞的比例,并测定患者治疗前后血清ACA指标、B超检查胚胎发育情况等.结果:治疗组患者治疗前CD4+CD25+FOXP3+Treg细胞的比例显著低于正常妊娠对照组(P<0.01);治疗后,其细胞比例显著高于治疗前(P<0.01).27例患者中20例ACA阳性的转阴率达85.00%,7例ACA定量滴度较治疗前显著下降(P<0.0l).保胎的成功率达92.59%.结论:ACA阳性先兆流产患者外周血CD4+CD25+ FOXP3 +Treg细胞的比例低于正常妊娠妇女,存在免疫调节异常;安子合剂治疗ACA阳性先兆流产的作用机理之一与增加CD4+ CD25+ FOXP3+ Treg细胞的比例、调节妊娠期机体免疫功能有关.%Objective; To observe the effect of Anzi Mixture on immune regulation of CD4+CD25+FOXP3+Treg cells in ACA -positive patients with threatened abortion. Methods: Selecting ACA-positive patients with threatened abortion as treatment group (27cases) , 125ml Anzi Mixture were given, 2 times a day, consecutive administrated for 4 weeks; selecting normal pregnant women as the control group ( 15cases). Detecting the percentage of peripheral blood CD4+CD25+FOXP3+Treg cells in the two groups, detecting the indicators of ACA before and after treatment by Anzi Mixture, B-ultrasound embryo development and so on. Results; Before treatment, the proportion of CD4+CD25+FOXP3+Treg cells in ACA-positive patients with threatened abortion was significantly lower than the control group (P<0. 01) ; after treatment of Anzi Mixture, the proportion of CD4+CD25+FOXP3+ Treg cells was significantly higher than before treatment (P<0. 01 ). The ACA negative rate of the qualitative indicators was 85. 00% , 7 cases of

  1. 3种不同中医证型艾滋病患者外周血CD+4CD+25调节性T细胞的表达%Expression of CD+4CD+25 regulatory T cell in peripheral blood of HIV/AIDS patients with different TCM syndromes

    Institute of Scientific and Technical Information of China (English)

    陈晓蓉; 杨宗国; 沈芳; 王江蓉; 卢洪洲; 杨悦娅

    2011-01-01

    objective: To observe the expression level of CD4+CD25+ regulatory T cell in peripheral blood of HIV/AIDS patients with different TCM syndromes, and to probe the immune negative regulation ability of HIV/AIDS. Methods: Based on the symptoms,signs,tongue manifestations, pulse conditions of AIDS patients, according to the thought of TCM Treatment with syndrome differentiation ,we divided the 97 HIV/AIDS patients into 3 different syndrome type, deficiency of pulmonary and renal syndrome, qi asthenia and blood stasis syndrome, and deficiency of spleen and renal syndrome, in order to observe the expression level of CD4+ CD25+ regulatory T cell in peripheral blood of HIV/AIDS patients with different TCM syndromes and 30cases of normal in control group. Results: The statistical significance of the expression level of CD4+ CD25+ regulatory T cell was observed among the 3 kinds of syndrome and control group (P<0.001). The deficiency of spleen and renal syndrome own the highest expression level of CD4+CD25+ regulatory T cell, followed by deficiency of pulmonary and renal syndrome, and qi asthenia and blood stasis syndrome. Conclusion: The expression level of CD4+CD25+ regulatory T cell of HIV/AIDS patients with different TCM syndromes has being reduced gradually from the deficiency of spleen and renal syndrome, to the deficiency of pulmonary and renal syndrome, and to the qi asthenia and blood stasis syndrome.%目的:观察不同中医证型艾滋病患者CD+4CD+25调节性T细胞(以下简称CD+4CD+25T细胞)的表达水平,探讨不同证型艾滋病免疫负调节能力.方法:根据艾滋病患者的症状、体征、舌象、脉象,按照中医辨证论治思路,分为肺肾不足、气虚血瘀、脾肾亏虚3种证型,设正常对照组30名,收集病例97例,观察不同证型艾滋病患者及正常对照组外周血CD+4CD+25T细胞的表达水平.结果:正常对照组、脾肾亏虚、肺肾不足、气虚血瘀各组患者CD+4CD+25T细胞的表

  2. IKK2dn转染树突状细胞诱导产生的CD4+CD25-T细胞的筛选及鉴定%Screening and function identification of CD4 + CD25 - T cells induced by immature dendritic cells transfected with IKK2dn

    Institute of Scientific and Technical Information of China (English)

    樊彩斌; 张东兴; 温端改; 侯建全; 欧阳骏; 杜科霖

    2012-01-01

    Objective To investigate the method of screening CD4 + CD25 - T cells from regulatory T cells (Treg) induced by recipient-derived immature dendritic cells (imDC) transfected by IKK2dn and loaded with donor antigens,and assess their immunologic function.Methods Rat bone marrow-derived imDC were transfected by IKK2dn and loaded by BN antigen,then cultured with Lewis rats T cells in vitro.From these Treg,CD4 + CD25 T cells were screened by magnetic active cell sorting (MACS),then incubated in secondary mixed lymphocyte reaction ( MLR),with Lewis rat T lymphocytes.Results By MACS,the purity of CD4 + CD25 - T cells was more than 95%.The result of secondary MLR displayed the absorbance value was significantly lower in the CD4 + CD25 - T cells group ( 0.106 ± 0.006 ) than that in BN antigen group (0.189 ± 0.007 ),Adv0-CD4 +T cells group (0.419 ± 0.014) and the third donor group (0.200 ± 0.008) (P <0.05).Conclusion By MACS sereening,we can obtain high purity of CD4 + CD25-T cells from Treg induced by imDC transfected with IKK2dn and loaded by BN rat antigen and recipient Lewis rats T cells.And these T cells can inhibit T cell proliferation with the donor antigen specificity.%目的 探讨从转染IKK2dn并负载供者抗原的未成熟树突状细胞(imDC)诱导产生的调节性T细胞(Treg)中筛选CD4+ CD25 - Treg的方法,并进行鉴定.方法 Lewis大鼠骨髓源性imDC,转染IKK2dn后负载供者BN大鼠抗原,与Lewis大鼠T细胞进行体外混合淋巴细胞反应(MLR)诱导产生Treg,用免疫磁珠法(MACS)筛选出CD4+ CD25 -T细胞,流式细胞仪(FCM)检测细胞纯度.加入CD4+ CD25 -T细胞行再次MLR检测其抑制T细胞增殖的作用.结果 经MACS筛选,CD4+ CD25 -T细胞纯度为(95.78±1.25)%.再次MLR结果显示CD4+ CD25 -T细胞组的吸光度值为(0.106±0.006),低于BN抗原组(0.189±0.007)、Adv0-CD4+T细胞组(0.419±0.014)及第三方供者抗原组(0.200±0.008),差异有统计学意义(P<0.05).结论 转染IKK2dn并负载

  3. Effect of bacillus calmette-guerin on CD+4 CD+25 CDlo127 treg in asthmatic mouse%卡介苗对哮喘小鼠CD+4CD+25CDlo127Treg表达的影响

    Institute of Scientific and Technical Information of China (English)

    葛荣领; 张建华

    2011-01-01

    目的 探讨卡介苗干预对哮喘小鼠调节性T细胞(Treg)及T淋巴细胞凋亡的影响.方法 27只小鼠随机分为3组:哮喘组,干预组,对照组.哮喘组小鼠用卵清蛋白(OVA)、氢氧化铝腹腔注射致敏,OVA雾化吸入激发,干预组在致敏前BCG干预3次,对照组生理盐水代替OVA及氢氧化铝.流式细胞术检测外周血(记为培养前)及植物血凝素(PHA)刺激培养后的外周血单个核细胞中Treg的表达,Comet法检测T淋巴细胞凋亡率.结果 培养前:哮喘组与对照组比较Treg显著降低,干预组与哮喘组比较显著升高.培养后:哮喘组与对照组比较Treg显著降低,干预组与哮喘组比较显著升高.同组小鼠Treg培养前后的比较:哮喘组、干预组表达无改变,对照组表达明显升高.T淋巴细胞凋亡率,哮喘组明显低于对照组,干预组明显高于哮喘组.结论 哮喘小鼠存在Treg数量小足和分化障碍,BCG干预能促进其数量上升,并促进T淋巴细胞凋亡.%Objective To explore the effect of BCG intervention on expression of CD/ CD+4 CD+25 Treg and T lymphocyte apopto-sis in asthmatic mouse. Methods 27 mice were randomly divided into 3 groups, the asthma model group, the treatment group and the normal control group. The mice were sensitized by ovalbumin and AL( OH) 3 with intraperitoneal injection, challenged with atomization inhalation. The treatment group were treated 3 times with BCG subcutaneous injection before sensitization. The normal control group were treated with saline water taking the place of ovalbumin and AL( OH) 3. Treg in peripheral blood and PBMC were detected by flow cytome-try, PBMC were stimulated and cultured by PHA. Counted the apoptosis ratio of T lymphocyte by Comet Assay. Results In peripheral blood: Compared the asthmatic group with the control group, Treg decreased remarkably; Compared the treatment group with the asthmatic group, it increased obviously. In PBMC: Compared the asthmatic group with the

  4. Expression of mRNAs coding for the alpha 1 chain of type XIII collagen in human fetal tissues: comparison with expression of mRNAs for collagen types I, II, and III

    OpenAIRE

    1989-01-01

    This paper describes the topographic distribution of the multiple mRNAs coding for a novel human short-chain collagen, the alpha 1 chain of type XIII collagen. To identify the tissues and cells expressing these mRNAs, human fetal tissues of 15-19 gestational wk were studied by Northern and in situ hybridizations. The distribution pattern of the type XIII collagen mRNAs was compared with that of fibrillar collagen types I, II, and III using specific human cDNA probes for each collagen type. No...

  5. Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization

    Institute of Scientific and Technical Information of China (English)

    Yoshihiro Furuichi; Hirotake Tokuyama; Satoshi Ueha; Makoto Kurachi; Fuminori Moriyasu; Kazuhiro Kakimi

    2005-01-01

    AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T ceils in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining.RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBVspecific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n = 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells.CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T ceil response and may affect the quality of memory T cell pools. The elimination of Treg

  6. CD4+CD25+调节性T细胞及Foxp3表达与支气管哮喘发病的相关性研究%Study of Relationship between CD4+ CD25+ Regulator T Cells as well as Expression of Foxp3 and Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    刘春花; 刘恩梅

    2006-01-01

    CD4+CD25+调节性T细胞(CD4+CD25+Tr)在胸腺内发育,迁移到外周组织发挥功能,通过对自身抗原反应T细胞活化和增殖起负调节作用,保持自身稳定,抑制自身免疫性疾病以及哮喘和炎症性肠病等炎症性疾病的发生,并调控器官移植耐受和肿瘤免疫.近年发现Foxp3是CD4+CD25+Tr成熟、分化以及发挥功能的调节基因.作为小儿最常见的慢性疾病,支气管哮喘的免疫学发病机制尚不完全清楚,CD4+CD25+Tr与Foxp3表达在哮喘发病中的作用已引起人们的广泛关注,其研究结果将为进一步探讨哮喘的发病机制和寻找有效的治疗方法提供理论依据.

  7. CD4+CD25 + Foxp3+ T-reg cells play an important role in na(i)ve immune tolerance in rat liver transplantation%CD4+CD25+Foxp3+T-reg细胞在大鼠肝移植天然免疫耐受模型中的作用

    Institute of Scientific and Technical Information of China (English)

    肖江卫; 周彤; 王崇树; 魏寿江; 王城; 李敬东; 彭勇; 金先庆

    2010-01-01

    Objective To study the effect of CD4+ CD25+ Foxp3 + T-reg cells in na(i)ve immune tolerance using a rat liver transplantation model, we monitored the changes of this population cell of CD4+ CD25+ Foxp3+ T-reg cells in liver、thymus、spleen and blood by flow cytometry technique. Methods Na(i)ve immune tolerance model of rat liver transplantation was established (LEW→DA) ,The rejection group (DA→LEW) was used as the control group. CD4+ CD25+ Foxp3+ T-reg cells were respectively extracted and measured in liver、thymus、 spleen and blood. Simultaneously, we recorded the survival rate of rats and liver graft pathological changes in every group. The expression level of Foxp3 mRNA in every group was monitored. Results DA rat in tolerance group could acquire long-time survival without any immunosuppressive drug. Compared with rejection group,CD4+ CD25+ Eoxp3+ T-reg cells in tolerance group were significantly increased, especially in blood. The expression level of Foxp3 mRNA is significantly higher(P2个月),且排斥组大鼠最多只能存活7~10d,免疫耐受组在肝脏、外周血、脾脏和胸腺单核细胞中CD4+CD25+Foxp3+T-reg细胞亚群所占的比例明显高于排斥组(P<0.05),且在移植肝脏中,免疫耐受组的Foxp3 mRNA表达含量明显高于排斥组.结论 在LEW→DA的大鼠免疫耐受模型中,CD4+CD25+Foxp3+T-reg细胞亚群细胞数量和比例明显升高,提示CD4+CD25+Foxp3+T-reg细胞亚群在移植免疫耐受过程中发挥着重要作用,从而为我们临床诱导免疫耐受提供一条新的思路.我们可以通过体外扩增抗原特异性的天然存在的调节性T细胞来抑制效应T细胞的激活和扩增,从而帮助诱导移植免疫耐受和抑制移植物排斥.

  8. 支气管哮喘患者外周血CD4+ CD25+调节性T细胞水平及Foxp3 mRNA表达的分析%CD4+ CD25+ regulatory T cells and expressions of forkhead/winged helix transcription factor ( Foxp 3 ) mRNA in peripheral blood of patients with asthma

    Institute of Scientific and Technical Information of China (English)

    薛克营; 周咏明; 熊盛道; 熊维宁

    2006-01-01

    目的 观察支气管哮喘(哮喘)患者外周血单个核细胞(PBMCs)中CD4+ CD25+调节性T细胞(Treg)水平及叉状头/翅膀状螺旋转录因子(Foxp3)mRNA表达的变化,探讨CD4+ CD25+ Treg在哮喘发病中的作用.方法采用流式细胞仪检测78例哮喘患者(急性发作期组30例,慢性持续期组25例,缓解期组23例)和29例健康志愿者(正常对照组)PBMCs中CD4+ CD25+ Treg的比例;反转录-聚合酶链反应(RT-PCR)检测PBMCs中Foxp3 mRNA的表达.结果 急性发作期组和慢性持续期组PBMCs中CD4+ CD25+ Treg的比例及Foxp3 mRNA的表达明显低于缓解期组和正常对照组(P<0.05);缓解期组CD4+ CD25+ Treg的比例及Foxp3 mRNA的表达虽亦低于正常对照组,但差异无统计学意义(P>0.05);急性发作期组CD4+ CD25+ Treg的比例及Foxp3 mRNA的表达低于慢性持续期组(P<0.05).结论 哮喘患者外周血中具有免疫抑制活性的CD4+ CD25+ Treg数量减少,功能下降,可能参与哮喘的发生和发展.

  9. 卡介苗多糖核酸对哮喘大鼠淋巴液和血液CD4+CD25+Foxp3+调节性T细胞的影响%The effect of BCG-PSN on CD4+CD25+Foxp3+Treg in blood and lymph of asthma rats

    Institute of Scientific and Technical Information of China (English)

    石涛; 冯学斌; 赵志旭; 张瑾锦

    2010-01-01

    目的:探讨卡介苗多糖核酸(BCG-PSN)对哮喘大鼠淋巴液和血液调节性T细胞数量及功能的影响.方法:将SD大鼠随机分为对照组、哮喘组和BCG-PSN组,分别收集不同时间点大鼠淋巴液和血液,采用流式细胞仪(FCM)检测CD4+CD25+Foxp3+调节性T细胞(CD4+CD25+Foxp3+Treg)百分率,酶联免疫吸附试验(ELISA)检测淋巴液和血浆白介素10(IL-10)和转录生长因子β1(TGF-β1)浓度.结果:各组在各时间点其淋巴液中CD4+CD25+Foxp3+Treg百分率、IL-10水平均较血液明显升高.哮喘组大鼠淋巴液和血液中CD4+CD25+Foxp3+Treg百分率、IL-10 、TGF-β1浓度均较对照组显著降低(P<0.05).BCG-PSN组淋巴液和血液中CD4+CD25+Foxp3+Treg百分率和IL-10水平较哮喘组明显升高(P<0.05),与对照组比较无显著性差异;而TGF-β水平在48小时较对照组和哮喘组明显升高(P<0.05).结论:哮喘大鼠淋巴液和血液存在明显CD4+CD25+Foxp3+Treg数量及功能不足.BCG-PSN可能通过增加哮喘大鼠外周血和淋巴液中CD4+CD25+Foxp3+Treg的数量及其产生IL-10和TGF-β水平,增强免疫抑制效应,从而发挥抑制哮喘炎症的作用.

  10. The role of CD4+CD25+ regulatory T cells in the pathogenesis of asthma in children%CD4+CD25+调节性T细胞在儿童哮喘发病机制中的作用初探

    Institute of Scientific and Technical Information of China (English)

    祖莹; 李成荣; 郑跃杰; 邓继岿; 付晓玲

    2006-01-01

    目的探讨哮喘急性发作患儿CD4+CD25+调节性T(Tr)细胞数量变化及影响其发育成熟的因素.方法观察20例哮喘患儿及相同数量同龄对照组.用流式细胞术检测外周血单个核细胞(PBMC)CD4、CD25表面标志及CD4+CD25+细胞内白细胞介素(IL-10)和转化生长因子受体(TGF-β)表达.用逆转录-聚合酶链反应(RT-PCR) 和荧光定量聚合酶链反应(Real-time PCR)检测PBMC Foxp3及SOCS1 mRNA表达.结果急性发作期哮喘患儿CD4+CD25+Tr细胞百分率(6.5%±1.9%)明显低于同龄对照组(12.0%±2.3%),P<0.01 ;CD4+CD25++IL-10及CD4+CD25++TGF-β分泌细胞亦明显低于对照组.Foxp3及SOCS1mRNA表达也显著降低( Foxp3:0.12±0.05 vs 1.71±0.58,P<0.001;SOCS1:0.38±0.19 vs 2.14±0.41,P<0.001).结论哮喘患儿CD4+CD25+Tr细胞明显降低可能参与哮喘发病,Foxp3及SOCS1表达降低可能是导致CD4+CD25+Tr细胞发育障碍的重要因素.

  11. Study of expression of CD25 and CXCR3 on T lymphocytes from patients with HCV/HIV co-infection or HIV mono-infection in China%中国HGV/HIV合并感染者或HIV单一感染者T淋巴细胞表面CD25和GXCR3表达的研究

    Institute of Scientific and Technical Information of China (English)

    康辉; 王亚男; 范霞; 姜拥军; 刁莹莹; 尚红

    2006-01-01

    [Objective] To investigate expression and significance of CD25 and CXCR3 on T lymphocytes from peripheral blood mononuclear cells (PBMC) in HCV mono-infection, HIV mono-infection and HCV/HIV co-infection. [Methods] PBMC were isolated from patients with HCV infection (n=21), HIV infection (n=14), HCV/HIV coinfection (n=28) and normal control (n=30). The CD4 and CD8 absolute count, proportion of CD25+CD4+ T cells, and expression of CXCR3 on CD4+ and CD8+ T cells from PBMC were analyzed by flow cytometry. [Results] A lower proportion of CD4+CD25+ T lymphocytes were found in HIV infection and HCV/HIV co-infection (P <0.001), while slight but not significant increased proportion of CD4+CD25+ T lymphocytes were detected in HCV infection. The expression of CXCR3 on CD4+T cells from PBMCs decreased significantly, but the expression of CXCR3 on CD8+T cells increased significantly in HIV and HCV/HIV co-infection (P <0.001). The expression of CXCR3 on CD4+T cells as well as CD8+T cells from PBMCs increased but not significantly in HCV infection. [Conclusion] Results suggested that the expression of CD25 and CXCR3 on T lymphocytes from PBMC were altered and immune regulatory function would be effected in HIV infection in China.%目的探讨T淋巴细胞表面CD25分子和趋化因子受体CXCR3,在丙肝病毒(HCV)单一感染,艾滋病病毒(HIV)单一感染和HCV/HIV合并感染过程中的表达及意义.方法分离HCV感染组(n=21),HIV感染组(n=14),HCV/HIV感染组(n=28)及正常对照组(n=30)人外周血单个核细胞.采用流式细胞术,计数CD4+和CD8+T淋巴细胞数,检测外周血CD4+CD25+T细胞百分含量和CD4+和CD8+T淋巴细胞表面CXCR3的表达水平.结果CD4+T细胞表面CD25的表达在HCV感染组轻度升高,而在HIV感染组及HCV/HIV合并感染组CD25的表达显著降低(P<0.001).HIV感染组及HCV/HIV合并感染组CD4+T细胞表面CXCR3表达显著降低(P<0.001),CD8+T细胞表面CXCR3表达显著升高(P<0.001);HCV感染组CD

  12. CD4+CD25+Foxp3+调节性T细胞与IL-33在儿童哮喘发病机制中的作用%Roles of CD4+CD25+Foxp3+ regulatory T cells and IL-33 in the pathogenesis of asthma in children

    Institute of Scientific and Technical Information of China (English)

    潘珍珍; 李羚; 郭赟; 贺建

    2014-01-01

    ObjectiveTo study the roles of CD4+CD25+Foxp3+ regulatory T cells (Treg) and IL-33 in the pathogenesis of asthma in children.MethodsFlow cytometry was used to detect peripheral blood CD4+CD25+Foxp3+Treg proportion in CD4+T lymphocytes in.45 children with asthma, 50 children with wheezing caused by respiratory syncytial virus infection and 40 healthy children. Serum levels of IFN-γ, IL-4, IL-5 and IL-33 were measured using ELISA.ResultsThe level of peripheral blood CD4+CD25+Foxp3+Treg in the asthma group was significantly lower than in the wheezing and control groups (P<0.05). In contrast, serum levels of IL-33 in the asthma group was signiifcantly higher than in the wheezing and control groups (P<0.05). Peripheral blood CD4+CD25+Foxp3+Treg level was negatively correlated with serum IL-33 level in the asthma group(r=-0.156,P<0.01). ConclusionsCD4+CD25+Foxp3+Treg may interact with IL-33 in the pathogenesis of childhood asthma.%目的:探讨CD4+CD25+Foxp3+调节性T细胞(Treg)与IL-33在儿童哮喘发病中的作用。方法采用流式细胞仪检测45例哮喘患儿(哮喘组)、50例呼吸道合胞病毒感染喘息患儿(喘息组)及40例健康儿童(对照组)外周血CD4+CD25+Foxp3+Treg细胞百分比,采用ELISA法检测各组外周血血清IFN-γ、IL-4、IL-5及IL-33浓度,进行比较分析。结果哮喘组患儿体内CD4+CD25+Foxp3+Treg 水平较喘息组及对照组均降低(P<0.05);哮喘组患儿体内IL-33水平较喘息组及对照组均升高(P<0.05),哮喘组患儿体内CD4+CD25+Foxp3+Treg与IL-33呈负相关(r=-0.156,P<0.01)。结论在哮喘患儿发病机制中,CD4+CD25+Foxp3+Treg与IL-33可能存在相互作用。                                                                             [中国当代儿科杂志,2014,16(12):1211-1214

  13. The level of CD4+CD25nt/hiCD127lo regulatory T cells and its clinical significance in children with asthma%哮喘患儿外周血 CD4+CD25nt/hi CD127lo调节性T细胞的测定及临床意义

    Institute of Scientific and Technical Information of China (English)

    湛洁谊; 卢慧敏; 林穗玲

    2016-01-01

    Objective To explore the proportion change of CD4+ CD25nt/hi CD127lo regulatory T cells(Treg)in pe-ripheral blood of children withasthma and to analyze its significance.Methods 150 asthmatic children were divided into three groups according to their clinicalfeatures:50 subjects in acute asthma attack group,50 subjects in clinical remis-sion of asthma group and 50 subjects in cough variant asthma group,meanwhile,50 healthy children were enrolled in the control group.The levels of CD4+ CD25nt/hi CD127lo Treg in peripheral blood of all children were detected by flow cy-tometer.Results The CD4+ CD25nt/hi CD127lo Treg level in acute attack group were lowest of the four groups (P 0.05).Conclusion The CD4+ CD25nt/hi CD127lo regulatory T cells may be involved in the pathogenesis of asthma,The level of CD4+ CD25nt/hi CD127lo regulatory T cells correlated with the severity of asthma in children.%目的:探讨 CD4+ CD25nt/hi CD127lo 调节性 T 细胞在哮喘儿童外周血中的比例改变,并探讨其临床意义。方法150例哮喘患儿按临床表现分为急性发作组(50例)、临床缓解期组(50例)和咳嗽变异性哮喘组(50例),另选择50名健康儿童为正常对照组。应用流式细胞仪检测上述各组外周血 CD4+ CD25nt/hi CD127lo 调节性 T 细胞占 CD4+ T细胞的百分比。结果急性发作期组患儿外周血 CD4+ CD25nt/hi CD127lo 调节性 T 细胞水平较缓解组、咳嗽变异性哮喘组及健康对照组明显下降(P <0.05),而缓解期组及咳嗽变异性哮喘组与健康对照组比较差异无统计学意义(P >0.05)。结论CD4+ CD25nt/hi CD127lo 调节性 T 细胞可能参与了哮喘的发生与发展,哮喘的严重程度可能与 CD4+CD25nt/hi CD127lo 调节性 T 细胞的水平相关。

  14. Research progress of CD4+CD25+ regulatory T cell in bone marrow hematopoietic system diseases%CD4+CD25+调节性T细胞在骨髓造血系统疾病中的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘增慧; 李勇华

    2011-01-01

    CD4 + CD25 + regulatory T cell is a unique T-cell subsets with immune regulation function. Natural CD4+CD25 + regulatory T cell originates from the thymus and acquired CD4+CD25 + regulatory T cell can be induced from CD4* CD25 - T cells in peripheral blood. A specific transcription inhibicory factor-foxp3 , can be expressed in its molecule surface, besides, it also can express other membrane molecules, such as CD4, CD25, CTLA-4 ( CD152), GITR, CD103, CD62L, CD69, CD134, CD71, CD54, CD45RA , TGF-β1 , IL-10, glactin-1 , neuropilin-1 , etc. Its main function is immunosuppression and immune anergy. Recent research finds that it overexpresses in acute myeloid leukemia, chronic lymphocytic leukemia and high-risk myelodysplastic syndrome. However, in aplastic anemia its expression is much lower than normal. Other researchers believe that it has much to do with acute graft versus host disease, in its occurrence and development. In this article, we will review the recent research results of CD4 + CD25 + regulatory T cell in bone marrow hematopoietic system diseases, specifically, in leukemia, acute graft versus host disease, aplastic anemia, myelodysplastic syndrome and multiple myeloma.%CD4+CD25+调节性T细胞(regulatory T cell, Treg)是具有独特免疫调节功能的T细胞亚群. 天然CD4+CD25+ Treg起源于胸腺,外周血中CD4+CD25-T细胞亦可诱导产生.其分子表面表达特异性的转录抑制因子Foxp3,还表达CD4、CD25、CTLA-4(CD152))、GITR、CD103、CD62L、CD69、CD134、CD71、CD54、CD45RA、TGF-β1、IL-10、半乳糖结合蛋白(glactin)-1、神经菌毛素(neuropilin)-1等膜分子,具有免疫抑制和免疫无能作用.近年来研究发现,急性髓细胞白血病(acute myeloid leukemia,AML)、慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)、高危骨髓异常增生综合征(myelodysplastic syndrome, MDS)患者Treg表达异常增高,而在再生障碍性贫血(aplastic anemia,AA)患者表达明显降低,其异常表达

  15. HIV慢性感染者Vδ2T淋巴细胞的CD25表达与其凋亡及疾病进展的关系研究%Correlations between CD25 expression on Vδ2 T lymphocytes and the apoptosis of T lymphocytes and disease progression in chronically HIV-infected patients

    Institute of Scientific and Technical Information of China (English)

    许文; 黄磊; 谢杨新; 秦恩强; 石磊; 武晓丽; 杨俊连; 杨欣欣; 赵敏

    2013-01-01

    Objective To investigate the correlations between CD25 expression on Vδ2 T lymphocytes and the frequency and apoptosis of Vδ2 T lymphocytes and disease progression in chronically HIV-infected patients.Methods Thirty-one chronically HIV-infected outpatients treated in our hospital from Mar.2012 to Apr.2013 and 10 healthy controls (HC) were enrolled in the study.Of 31 chronically HIV-infected patients,10 didn't receive highly active antiretroviral therapy (HAART) (without HAART group),10 received 3 months of HAART (3-month HAART group),and 11 received 6 months of HAART (6-month HAART group).The frequency and apoptosis of Vδ2 T lymphocytes and CD25 expression on Vδ2 T lymphocytes were detected by flow cytometry.The changes of the above-mentioned indicators of without HAART group,3-month HAART group and 6-month HAART group were observed respectively,and the correlations between these indicators and CD4+ T lymphocyte counts and viral loads of each group were analyzed respectively.The correlations between CD25 expression and the frequency and apoptosis of Vδ2 T lymphocytes were analyzed as well.Results CD25 expression on Vδ2 T lymphocytes in chronically HIV-infected patients increased significantly as compared with HC.Though 6 months of HAART could down-regulate it,the expression was still higher than that of HC.CD25 expression on Vδ2 T lymphocytes decreased along with the increase in CD4+ T lymphocyte counts,but the correlation was not significant.The correlation between CD25 expression on Vδ2 T lymphocytes and viral loads in the patients not receiving HAART was not significant.The frequency of Vδ2 T lymphocytes was negatively correlated with CD25 expression in chronically HIV-infected patients,but the correlation between the apoptosis of and CD25 expression on Vδ2 T lymphocytes was not significant.Conclusions Vδ2 T lymphocytes are activated in chronically HIV-infected patients,which may be correlated with the decline in the frequency of Vδ2 T lymphocytes

  16. Expression and significance of CD4 + CD25 + CD127 - regulatory T Cells in patients with chronic hepatitis C viral infection%慢性丙型肝炎患者中CD4+ CD25+ CD127-调节性 T 细胞的表达及意义

    Institute of Scientific and Technical Information of China (English)

    韩荔芬; 林国贤; 陈怡; 陈清; 邱荣仙; 郑玲

    2015-01-01

    Objective To explore the expression of CD4 + CD25 + CD127 - regulatory T Cells from patients with chronic hepatitis C viral infection,and to evaluate its clinical significance. Methods 67 patients with HCV and 32 healthy volunteers were included in this study. The proportion of CD4 + CD25 + CD127 - regulatory T cells in peripheral blood was detected by using flow cytometry. HCV RNA detection in the pe-ripheral blood of HCV patients were done by real - time fluorescent quantitative PCR. Results Comparing with healthy controls,drug abusing and non - drug abusing HCV - infected patients in peripheral blood had a lower percentage of CD4 + CD25 + CD127 - regulatory T cells. The proportion of CD4 + CD25 + CD127 - regulatory T cells to CD4 + T cells in peripheral blood from drug abusing and non - drug abusing HCV - infected patients (4. 44% ± 1. 67% )account for(3. 84% ± 1. 95% )and(4. 44% ± 1. 67% )respectively,which was significantly lower than those from healthy controls(6. 10% ± 1. 65% )( P 0. 05);The expression of CD4 + CD25 + CD127 - regulatory T cells in HCV group before antiviral treatment was evident-ly lower than that in treated HCV group and control group( P < 0. 01). Conclusion The expression of CD4 + CD25 + CD127 - regulatory T cells in the antiviral treatment HCV patients was evidently higher than those of untreated HCV patients,which explained that the regulatory T cell possi-bly hold a role in the activation of the immune response to HCV infection. In addition,the expression level of CD4 + CD25 + CD127 - regulatory T cells in peripheral blood may be monitoring the patientˊs body cell immune status and become the index of body anti - virus immune response.%目的:探讨 CD4+ CD25+ CD127-调节性 T 细胞在慢性丙型肝炎(HCV)患者中的表达及其临床意义。方法收集 HCV 患者67例,并根据是否吸毒分为吸毒丙肝组35例和非吸毒丙肝组32例;健康体检人员32例作为对照。采用流式细

  17. The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo

    OpenAIRE

    Doganci, Aysefa; Eigenbrod, Tatjana; Krug, Norbert; De Sanctis, George T.; Hausding, Michael; Erpenbeck, Veit J.; Haddad, El-Bdaoui; Schmitt, Edgar; Bopp, Tobias; Kallen, Karl-J.; Herz, Udo; Schmitt, Steffen; Luft, Cornelia; Hecht, Olaf; Jens M Hohlfeld

    2005-01-01

    The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we investigated the role of IL-6R components in asthma. We observed increased levels of sIL-6R in the airways of patients with allergic asthma as compared to those in controls. In addition, local blockade of the sIL-6R in a murine model of late-phase asthma after OVA sensitization by gp130–fraction ...

  18. Detection of CD4+/CD8+T Lymphocyte Ratio and CD4+CD25+ Treg in Peripheral Blood of Patients with Sporadic Vitiligo%散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+T细胞的检测

    Institute of Scientific and Technical Information of China (English)

    叶蓉; 马刚; 胡小平; 彭曦

    2012-01-01

    目的 检测散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+调节性T细胞水平,探讨其与散发型白癜风发病的关系.方法 散发型白癜风患者29例,男13例,女16例.通过流式细胞仪对散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+调节性T细胞水平进行检测,并与20例健康人相比较.结果 与健康对照组相比,散发型白癜风患者外周血中CD4+/CD8+T细胞比值的差异无统计学意义(P>0.05),而CD4+CD25+调节性T细胞水平明显减少,差异有统计学意义(P<0.05),但在不同病程的患者中CD4+CD25+调节性T细胞数量的差异无统计学意义(P>0.05).结论 散发型白癜风患者外周血中存在CD4+CD25+调节性T细胞水平下降,可能与散发型白癜风的发生发展有一定关系.%Objective To detect the CD4+/CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level in peripheral blood of patients with sporadic vitiligo, and to investigate its role in the pathogenesis of sporadic vitiligo. Methods Peripheral blood samples were taken from 29 outpatients with sporadic vitiligo, including 13 males and 16 females. The CD4+/CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level was detected in peripheral blood of patients with sporadic vitiligo by flow cytometry, as well as controlled samples from 20 healthy human. Results There was no difference on the ratio of CD4+/CD8+ T lymphocyte between the patients with sporadic vitiligo and healthy people (P>0.05). Compared to the controlled group, the proportion of CD4+CD25+ Treg was significantly lower in sporadic vitiligo patients(P0.05). Conclusion The level of CD4+CD25+ Treg is lower in peripheral blood of sporadic vitiligo patients, which might play a role in the pathogenesis and development of sporadic vitiligo.

  19. Influences of Inhaled Corticosteroids on CD4+ CD25+ Regulatory T Cells and Foxp3 mRNA of Asthmatic Patients%吸入激素对哮喘患者外周血CD4+CD25+调节性T细胞水平及Foxp3mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    薛克营; 柯明耀; 姜燕; 陈玲玲; 吴雪梅; 谢红旗

    2011-01-01

    目的 观察支气管哮喘患者外周血CD4 CD25调节性T细胞(CD4CD25Treg)、Foxp3 mRNA的水平及吸入糖皮质激素对其的影响.方法 流式细胞仪检测非急性发作期哮喘患者吸入激素前、后和健康志愿者(正常对照组)外周血单个核细胞(PBMCs)中CD4CD25Treg的比例,RT-PCR检测Foxp3 mRNA表达变化,肺功能仪检测第1秒用力呼气容积占预计值百分比(FEV.%pred)和呼气峰流量(PEF).结果 哮喘组治疗前CD4CD25Treg水平及Foxp3 mRNA的表达显著低于正常对照组(PCD25Treg水平及Foxp3 mRNA的表达较治疗前显著升高(P%pred、PEF显著低于正常对照组(P%pred、PEF较治疗前显著增加(PCD25Treg数量减少,功能下降,参与了哮喘的发病过程;吸入激素可以上调哮喘患者外周血CD4CD25Treg及Foxp3 mRNA的水平,改善哮喘患者的肺功能.%Objective To investigate the percentage of CD4+ CD25+ Treg cells and expression of Foxp3 mRNA in asthmatic patients and the impacts of inhaled steroids.Methods The percentages of CD4 + CID25 + Treg cells was assayed by flow cytometry and the expression of Foxp3 mRNA was detected by RT-PCR in peripheral blood mononuclear cells from the patients with chronic persistent asthma before and after steroids inhalation in comparison with healthy control.The forced expired volum in one second/predicted value( FEV1 % pred)and peak expired flow (PEF) were measured by spirometry.Results The level of CD4 + CD25 + Treg cells and the expression of Foxp3 mRNA were lower in asthmatics before steroids treatment than those in control ( P < 0.05 ) which were increased significantly after steroids treatment ( P < 0.05 ).FEV1 % pred and PEF were declined significantly than those in control but improved markedly after treatment (P < 0.05 ).Conclusions The insufficiency of amount and function of immue-suppressive CD4 + CD25 + Treg cells may play a role in the pathogenesis of asthma.Inhaled steroids can improve the lung function of asthmatics

  20. 抗CD3单克隆抗体对人CD4+CD25+T淋巴细胞凋亡和自噬的影响%Apoptosis and autophagy induced by anti-CD3 monoclonal antibody in human peripheral blood CD4+CD25+T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    邬伟明; 洪国斌; 徐晓华

    2009-01-01

    目的 观察抗CD3单克隆抗体对分离培养的人外周血CD4+CD25+T淋巴细胞自噬、凋亡及其分泌的代表性因子转化生长因子β(TGF-β)的影响.方法 采用密度梯度离心法及尼龙棉柱法分离32例健康者外周血T淋巴细胞,磁性细胞分离器(MACS)分离得到CD4+CD25+T淋巴细胞,分别利用电镜及流式细胞仪观察、检测各组(抗CD3单克隆抗体1 mg/L组、IgG1同型抗体对照组)干预72 h后细胞的凋亡率、自噬率,用ELISA法检测细胞培养上清液中细胞因子TGF-β的水平.结果 抗CD3单克隆抗体组CD4+CD25+T淋巴细胞自噬率、凋亡率及TGF-β水平均增加(均P0.05).结论 抗CD3单克隆抗体可促进CD4+CD25+T淋巴细胞凋亡和自噬及TGF-β分泌,且自噬与凋亡间相互独立.%Objective To observe the autophagy,apoptosis rate and TGF-β secretion in human peripheral blood CD4+CD25+T lymphocytes induced by anti-CD3 monoclonal antibody.Methods Peripheral blood T lymphocyte of 32 healthy adults were separated by Percoll (1.073 g/ml) and harvested by using nylon column.Then,CD4+CD25+T lymphocytes were isolated by (magnetic cell sorting MACS).The cultured cells were divided into different groups (anti-CD3 mAb group 1 mg/L,IgG1 isotype control group).The apoptosis and autophagy rate of the cells cultured for 72 h were analyzed by electron microscope and flow cytometry.The cell culture supernatants were collected after 72 h and analyzed for levels of TGF-β by ELISA.Results The autophagy,apoptosis rate and TGF-β secretion in human peripheral CD4+CD25+T lymphocytes of the health group were increased by anti-CD3 mAb(all P<0.01);There was no significant statistic difference in correlation between apoptosis and autophagy of T lmyphocytes.Conclusions Anti-CD3 mAb could increase the autophagy rate,apoptosis rate and TGF-β secretion of peripheral blood CD4+CD25+Tregs,and there was no significant statistic difference between autophagy and apoptosis of CD4+CD25+Tregs.

  1. OX40 stimulation down-regulates the expression of Foxp3 in CD4+ CD25+ regulatory T cells%OX40信号调节抑制小鼠CD4+CD25+调节性T淋巴细胞Foxp3的表达

    Institute of Scientific and Technical Information of China (English)

    马东霞; 王璐; 赵越; 向莹; 刘斌

    2013-01-01

    目的 探讨共刺激信号OX40对体外诱导的小鼠CD4+ CD25+适应性调节性T淋巴细胞(iTreg)的Foxp3表达的影响.方法 制备C57BL/6小鼠淋巴细胞悬液,经免疫磁珠法分选,获得CD4+ CD25-静息T淋巴细胞,与抗CD3单克隆抗体、抗CD28单克隆抗体、转化生长因子β1、白细胞介素2共孵育,诱导产生Foxp3+ iTreg.在此基础上,于培养体系中加入OX40激动型抗体及其对照抗体,利用流式细胞仪分析研究OX40信号刺激对iTreg Foxp3表达的影响.结果 C57BL/6小鼠淋巴结中CD4+ CD25+天然调节性T淋巴细胞(Treg)比例为(5.0±0.4)%,体外诱导培养的CD4+CD25+ Treg比例为(71.8±13.4)%,其中Foxp3阳性表达占(74.9±1.9)%.OX40激动型抗体组CD4+ CD25+ Treg细胞比例为(80.0±1.6)%,其中Foxp3表达水平为(59.2±0.7)%;OX40激动型抗体对照抗体组CD4+ CD25+ Treg细胞比例为(86.0±1.4)%,其中Foxp3表达水平为(70.0±0.8)%,两组间差异有统计学意义(P<0.05).结论 静息T淋巴细胞可以在体外诱导培养获得高纯度iTreg;OX40信号刺激可以显著抑制CD25+ iTreg细胞Foxp3的表达.%Objective To evaluate the regulatory effect of OX40 co-stimulatory signal on the expression of Foxp3 in inductive regulatory T cells (iTreg) in vitro.Method CD4+ CD25+ naive T cells were isolated from C57BL/6 mouse lymphocyte suspension by MASC CD4+ CD25+ regulatory T cell isolation kit.Inductive Tregs were generated by stimulation of naive T cells in the presence of transforming growth factor beta (TGFβ1),anti-CD3,anti-CD28 and IL-2.The regulatory effect on iTregs was shown by use of OX40 stimulation monoclonal antibody (OX86) or control antibody.Using flow cytometric analysis (FACS),we examined the antibody-based identification of Tregs surface markers CD4 and CD25,along with the intracellular activation marker FoxP3.Results The ratio of CD4+ CD25+ nTregs isolated from mouse lymphatic node was (5.0 ± 0.4)% vs.(71.8 ± 13.4)% of TGFβ1-driven i

  2. 老年脓毒症休克患者CD4+CD25+调节性T细胞的变化及对预后的影响%Effects of changes of CD4+ CD25+ regulatory T cells on prognosis in elderly patients with septic shock

    Institute of Scientific and Technical Information of China (English)

    呼邦传; 孙仁华; 徐云祥; 杨向红; 李茜; 韩芳

    2010-01-01

    目的 探讨老年脓毒症休克患者CD4+CD25+调节性T淋巴细胞(CD4+CD25+Treg)的变化及对预后的影响.方法 选择老年脓毒症休克患者75例,采用流式细胞仪检测患者外周血第1、4天和第7~10天CD4+CD25+叉头转录基因P3(FoxP3)/CD4+比例和白细胞DR抗原(HLA-DR)表达.结果 老年脓毒症休克患者平均年龄(69.2±7.5)岁,28 d病死率为53.3%.(1)休克死亡组与生存组CD4+CD25+FoxP3/CD4+比较,第1天(1.76±0.31)对(1.68±0.24)%,第4天(1.94±0.32)%对(1.82±0.28)%,差异均无统计学意义(P>0.05),第7~10天休克死亡组(2.65±0.28)%,明显高于存活组(1.79±0.27)%,差异有统计学意义(t=11.30,P<0.01);(2)死亡组第4天和第7~10天HLA-DR表达持续低下,显著低于生存组(t=7.29,t=16.80,均P<0.01),并分别与CD4+CD25+FoxP3/CD4+比例呈显著负相关(r=-0.39,P<0.05;r=-0.58,P<0.01);(3)多元Logistic回归分析显示,脓毒症休克患者第7~10天CD4+CD25+FoxP3/CD4+(OR=3.47,95%CI:1.33~10.0)和HLA-DR(OR=0.27,95%CI:0.14~0.73)是影响其死亡的独立危险因素.结论 老年脓毒症休克患者CD4+CD25+Treg持续上升,提示机体免疫功能抑制,脓毒症休克死亡的危险性增加.%Objective To investigate the changes of CD4+CD25+ regulatory T (Treg) cells in elderly patients with septic shock, and to evaluate the effects of the changes on 28-day mortality rate.Methods The 75 consecutive elderly patients with septic shock were recruited from December 2006to December 2008, and the general states and clinical characteristics of them were analyzed. The CD4+ CD25+ FoxP3 regulatory T cells and human leucocyte antigen DR (HLA-DR) were measured by flow cytometer at the 1st, 4th and 7-10th day of septic shock after being diagnosed. Results The patients were at an average age of (69.2±7.5) years, and the 28-day mortality rate was 53.3%.There were no significant differences in the percentage of CD4 + CD25+ FoxP3/CD4+T cells between the survivors and the non-survivors at

  3. A G {r_arrow} A transition at position IVS-11 +1 of the HEX A {alpha}-chain gene in a non-Ashkenazic Mexican Tay-Sachs infant

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, S.R.P.; Gwon, S.; DeGasperi, R. [New York Univ. Medical Center, NY (United States)] [and others

    1994-09-01

    Tay-Sachs disease (TSD) is an autosomal recessive storage disorder caused by a deficiency of the lysosomal enzyme, {beta}-N-acetylhexosaminidase A (Hex A), a heteropolymer composed of two polypeptides, {alpha} and {beta}. Mutations in the {alpha}-chain gene render the enzyme defective, resulting in the accumulation of g{sub m2} ganglioside in the nervous system. Deficiency of Hex A was detected in a non-Ashkenazic girl of Mexican origin indicating infantile onset of TSD. Molecular investigation of the {alpha}-chain gene excluded the typical Ashkenazic 4 bp insertion in the exon 11 and the intron 12 splice-junction mutations by Hae III and Dde I restriction analysis, respectively. Single strand conformation polymorphism (SSCP) analysis showed a different pattern in the sample where exon 11 and flanking regions were amplified in the patient DNA as compared to the migration of control DNA. Sequencing of PCR amplified genomic DNA containing exon 11 and flanking intronic regions showed a single base substitution (G {r_arrow} A) at position IVS-11 +1. This mutation creates a recognition site for the restriction enzyme Mbo II. Digestion of exon 11 and flanking regions with Mbo II demonstrated homozygosity of the patient for this mutation and heterozygosity in the mother. mRNA from cultured fibroblasts obtained from a normal control and from the propositus was reverse transcribed. The cDNAs coding for Hex A {alpha}-chain were amplified in four overlapping fragments. In the patient sample it was not possible to amplify the fragment containing the exon 11/intron 11 junction, indicating that this mutation alters normal RNA processing of the Hex A pre-mRNA resulting in the deficiency of Hex A activity.

  4. The potential role of cell surface complement regulators and circulating CD4+ CD25+ T-cells in the development of autoimmune myasthenia gravis

    OpenAIRE

    Hamdoon, Mohamed Nasreldin Thabit; Fattouh, Mona; El-din, Asmaa Nasr; Elnady, Hassan M.

    2016-01-01

    Introduction CD4+CD25+ regulatory T-lymphocytes (T-regs) and regulators of complement activity (RCA) involving CD55 and CD59 play an important role in the prevention of autoimmune diseases. However, their role in the pathogenesis of human autoimmune myasthenia gravis (MG) remains unclear. This study aimed to determine the frequency of peripheral blood T-regs and CD4+ T-helper (T-helper) cells and the red blood cells (RBCs) level of expression of CD55 and CD59 in MG patients. Methods Fourteen ...

  5. Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans.

    Directory of Open Access Journals (Sweden)

    Stephen M Todryk

    Full Text Available BACKGROUND: Immunity to malaria develops naturally in endemic regions, but the protective immune mechanisms are poorly understood. Many vaccination strategies aim to induce T cells against diverse pre-erythrocytic antigens, but correlates of protection in the field have been limited. The objective of this study was to investigate cell-mediated immune correlates of protection in natural malaria. Memory T cells reactive against thrombospondin-related adhesive protein (TRAP and circumsporozoite (CS protein, major vaccine candidate antigens, were measured, as were frequencies of CD4(+ CD25(high T cells, which may suppress immunity, and CD56(+ NK cells and gammadelta T cells, which may be effectors or may modulate immunity. METHODOLOGY AND PRINCIPAL FINDINGS: 112 healthy volunteers living in rural Kenya were entered in the study. Memory T cells reactive against TRAP and CS were measured using a cultured IFNgamma ELISPOT approach, whilst CD4(+ CD25(high T cells, CD56(+ NK cells, and gammadelta T cells were measured by flow cytometry. We found that T cell responses against TRAP were established early in life (<5 years in contrast to CS, and cultured ELISPOT memory T cell responses did not correlate with ex-vivo IFNgamma ELISPOT effector responses. Data was examined for associations with risk of clinical malaria for a period of 300 days. Multivariate logistic analysis incorporating age and CS response showed that cultured memory T cell responses against TRAP were associated with a significantly reduced incidence of malaria (p = 0.028. This was not seen for CS responses. Higher numbers of CD4(+ CD25(high T cells, potentially regulatory T cells, were associated with a significantly increased risk of clinical malaria (p = 0.039. CONCLUSIONS: These data demonstrate a role for central memory T cells in natural malarial immunity and support current vaccination strategies aimed at inducing durable protective T cell responses against the TRAP antigen. They also

  6. CD4+CD25+Treg细胞在慢性荨麻疹发病中的作用

    Institute of Scientific and Technical Information of China (English)

    冯欢; 郭胤仕

    2011-01-01

    CD4+CD25+Treg细胞的功能紊乱在变态反应性疾病发生发展中的作用日益引起人们的关注.新近研究表明慢性荨麻疹是由于Treg细胞数量和(或)功能上的异常所引发.文章阐述了Treg细胞的来源、分类、作用机制及其与慢性荨麻疹之间的关系.

  7. Inhibiting effect of Astragalus polysaccharides on the functions of CD4+CD25highTreg cells in the tumor microenvironment of human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Qiang; BAO Jian-min; LI Xiao-li; ZHANG Ti; SHEN Xiao-hong

    2012-01-01

    Background Astragalus polysaccharides (APS),the main active extract from Astragalus membranaceus (a traditional Chinese medicinal herb),is associated with a variety of immunomodulatory activities.The purpose of the present study was to examine the effect of APS on the function of Treg cells in the tumor microenvironment of human hepatocellular carcinoma (HCC) and to identify the pharmacologic mechanism of APS responsible for the anti-chemotactic activity in CD4+CD25highTreg cells in tumor site of HCC.Methods The prevalence of Treg in fresh tissue samples from 31 patients with HCC after radicalhepatectomy was detected.CD4,CD25 and CD127 were selected as Treg cell makers to phenotype cell populations.The expression of FOXp3 mRNA was also analyzed.The migration and proliferation of Treg cells were observed.Interleukin (IL)-4,IL-10,IFN-γ and SDF-1 in cell supernatant were detected.For all tests,functions of Treg cells were evaluated after treatment with APS.Results APS can inhibit the growth and proliferation of CD4+CD25+Treg cells in vitro in a dose- and time-dependent manner.APS may inhibit CD4+CD25+Treg cells through restoring the cytokine imbalance and reducing the expression of FOXp3 in local HCC microenvironments.SDF-1 played an important role in there recruitment of Treg cells into the tumor microenvironment of HCC.APS might have inhibiting effects on Treg cell migration by blocking SDF-1 or its receptor through the CXCR4/CXCL12 pathway.Conclusions The increase in numbers of tumor associated Treg cells might play a role in modulation of the immune response against HCC.APS can restore the cytokine balance in the tumor micro environment and suppress the expression of FOXp3 mRNA to inhibit the immune suppressive effects of Treg cells.The application of APS in the tumor microenvironment might act to enhance the anti-tumor effects of the immunotherapy-based methods,and consequently to increase the survival rate in HCC.

  8. Increased cytotoxicity of CD4+ invariant NKT cells against CD4+CD25hiCD127lo/− regulatory T cells in allergic asthma

    OpenAIRE

    Nguyen, Khoa D.; Vanichsarn, Chris; Nadeau, Kari C.

    2008-01-01

    CD4+CD25hiCD127lo/− regulatory T cells (Treg) have been implicated in the resolution of asthma-associated inflammation while the opposite role of CD4+ invariant NKT (iNKT) cells has been the subject of recent investigations. Studies here focused on mechanisms of interaction between CD4+ iNKT cells and Treg to further explore their roles in allergic asthma (AA). Flow cytometry analysis revealed a significant increase in the expression of the natural cytotoxicity receptors NKp30 and NKp46 by CD...

  9. Fel d 1-airway inflammation prevention and treatment by co-immunization vaccine via induction of CD4+CD25-Foxp3+ Treg cells

    OpenAIRE

    Pei, Yechun; Geng, Shuang; Liu, Lin; Yan, Fengxiang; Hong GUAN; Hou, Jian; Chen, Yongfu; Wang, Bin; An, Xiaorong

    2013-01-01

    Pet allergens are major causes for asthma and allergic rhinitis. Fel d 1 protein, a key pet allergen from domestic cat, can sensitize host and trigger asthma attack. In this study, we report that co-immunization with recombinant Fel d 1 protein (rFel d 1) plus plasmid DNA that contains Fe1 d 1 gene was effective in preventing and treating the natural Fel d 1 (nFel d 1) induced allergic airway inflammation in mice. A population of T regulatory cells (iTreg) exhibiting a CD4+CD25-Foxp3+ phenoty...

  10. XCL1 Enhances Regulatory Activities of CD4+CD25highCD127low/− T Cells in Human Allergic Asthma1

    OpenAIRE

    Nguyen, Khoa D.; Fohner, Alison; Booker, Jerome D.; Dong, Chen; Krensky, Alan M.; Nadeau, Kari C.

    2008-01-01

    Chemokine-mediated recruitment of regulatory cell subsets to the airway during inflammation and enhancement of their activities are potential strategies for therapeutic development in allergic asthma (AA). In this study, we aim to explore the role of XCL1, a chemokine associated with immune suppression and allergy, on CD4+CD25highCD127low/− regulatory T cell (Treg) function in AA. Flow cytometry and PCR analysis showed a reduction in XCL1 and XCR1 expression in AA Treg compared with healthy c...

  11. CD4+/CD25(high)/FoxP3+/CD127- regulatory T cells in bronchoalveolar lavage fluid of lung cancer patients.

    Science.gov (United States)

    Osińska, Iwona; Stelmaszczyk-Emmel, Anna; Polubiec-Kownacka, Małgorzata; Dziedzic, Dariusz; Domagała-Kulawik, Joanna

    2016-10-01

    The aim of the study was to compare the presence of regulatory T cells (Tregs) in the local lung cancer environment versus systemic immune response based on the examination of bronchoalveolar lavage fluid (BALf) and peripheral blood (PB) from the same patient. 35 patients with lung cancer were investigated. Flow cytometry method with panel of antibodies: anti CD4/CD25/FoxP3/CD127 for Tregs identification was used. We observed significantly higher proportion of Tregs in the BALF than in PB (median 9.4 vs. 5.4%, penvironment may have therapeutic relevance in individual indication for anti-cancer immune-therapies. PMID:27474372

  12. Practicing Qigong Baduanjin on drug addicts can reduce CD4+CD25+ regulatory T cells%习练健身气功八段锦降低戒毒人员CD4+CD25+调节性T细胞作用的研究

    Institute of Scientific and Technical Information of China (English)

    陈昌乐; 王艳; 李洁

    2014-01-01

    目的:通过比较习练健身气功八段锦前后,戒毒人员外周血中CD4+CD25+调节性T细胞(CD4+C D25+Treg)占CD4+T细胞的比例变化,研究健身气功八段锦提高戒毒人员免疫功能的分子机制.方法:80名戒毒人员随机分为健身气功八段锦习练组和对照组各40名.3个月后,流式细胞术法检测习练组和对照组外周血中CD4+CD25+T细胞、CD3+细胞、CD4+T细胞比例和CD4/CD8比值.免疫磁珠法分离并去除外周血中CD4+CD25+T细胞后,3H-TdR掺入法检测淋巴细胞增殖反应.结果:3个月后,习练组外周血中免疫抑制性CD4+CD25+T细胞比例明显低于对照组(P<0.05);而习练组外周血中CD3+细胞、CD4+T细胞、CD4/CD8细胞比例明显高于对照组(P<0.05).习练组外周血T淋巴细胞增殖反应明显高于对照组(P<0.05),免疫磁珠法去除CD4+CD25+T细胞后,对照组外周血T淋巴细胞增殖反应恢复至与习练组和健康对照组水平.结论:习练健身气功八段锦可降低戒毒患者外周血内CD4+CD25+Treg 比例,提高戒毒患者的免疫功能.

  13. 支气管哮喘患者外周血Th17、CD4+CD25+Treg细胞表达特征%The prevalence of blood Th17 and CD4+CD25+Treg cells in patients with bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    施宇衡; 时国朝; 万欢英; 蒋黎华; 艾香艳; 朱海星; 汤葳

    2010-01-01

    目的:探讨外周血Th17和CD4+CD25+调节性T细胞(Treg)在支气管哮喘患者中的表达特征.方法:41例慢性持续期哮喘患者,分为间歇-轻度组(n=23)和中重度组(n=18),行肺功能检查和哮喘控制问卷(ACQ)调查,20例正常人作为对照.通过流式细胞术检测外周血Th17和CD4+CD25+Treg细胞的比例.ELISA检测血浆以及植物血凝素刺激24小时后外周血单个核细胞(PBMC)上清液中的IL-17、IL-10、TGF-β水平.结果:中重度哮喘组外周血Th17细胞比例及血浆IL-17水平高于间歇-轻度哮喘和正常人组,而外周血CD4+CD25+Foxp3+Treg细胞比例及血浆IL-10、TGF-β水平则降低.中重度哮喘组PBMC上清液中IL-17水平增高.哮喘患者FEV1(%预计值)与Th17细胞及血浆IL-17表达成负相关,与CD4+CD25+Treg表达成正相关.ACQ平均得分与Th17细胞和血浆IL-17表达成正相关,与外周血CD4+CD25+Treg表达成负相关.结论:中重度哮喘中外周血Th17细胞应答增强,而CD4+CD25+ Treg细胞缺乏,哮喘的严重程度及症状控制与外周血Th17/Treg免疫应答失衡密切相关.

  14. Inter-alpha-trypsin inhibitor heavy chain 4: a novel biomarker for environmental exposure to particulate air pollution in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Lee KY

    2015-04-01

    Full Text Available Kang-Yun Lee,1–3 Po-Hao Feng,1,2 Shu-Chuan Ho,4 Kai-Jen Chuang,5,6 Tzu-Tao Chen,2,3 Chien-Ling Su,2,4 Wen-Te Liu,2,4 Hsiao-Chi Chuang2,4 1Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, 2Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, 3Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 4School of Respiratory Therapy, College of Medicine, Taipei Medical University, 5Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, 6School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan Abstract: Chronic obstructive pulmonary disease (COPD is a chronic inflammatory disease that is correlated with environmental stress. Particulate matter ≤10 µm (PM10 is considered to be a risk factor for COPD development; however, the effects of PM10 on the protein levels in COPD remain unclear. Fifty subjects with COPD and 15 healthy controls were recruited. Gene ontology analysis of differentially expressed proteins identified immune system process and binding as the most important biological process and molecular function, respectively, in the responses of PM10-exposed patients with COPD. Biomarkers for PM10 in COPD were identified and compared with the same in healthy controls and included proteoglycan 4 (PRG4, inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4, and apolipoprotein F (APOF. PRG4 and ITIH4 were associated with a past 3-year PM10 exposure level. The receiver operating characteristic curve analysis showed that ITIH4 is a sensitive and specific biomarker for PM10 exposure (area under the curve [AUC] =0.690, P=0.015 compared with PRG4 (AUC =0.636, P=0.083, APOF (AUC =0.523, P=0.766, 8-isoprostane (AUC =0.563, P=0.405, and C-reactive protein (CRP; AUC =0.634, P=0.086. ITIH4 levels were correlated with CRP (r=0

  15. 胃肠道癌肿患者外周血CD4+CD25+FOXP3+调节性T细胞的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    仇俊兰; 张惠; 曹斐; 吴惠莲; 皇甫照; 奉林

    2009-01-01

    目的:研究胃肠道癌肿患者外周血CD4+CD25+FOXP3+调节性T(Treg)细胞的表达,并探讨其临床意义。方法:通过免疫荧光术及流式细胞仪检测20例胃癌患者及20例结肠癌患者外周血CD4+CD25+FOXP3+Treg细胞、CD4+CD25+high Treg细胞、CD4+T细胞及CD4+ CTLA-4+T细胞。结果:胃癌组、结肠癌组与健康献血者比较外周血CD4+CD25+FOXP3+ Treg细胞、CD4+CD25+high Treg细胞及CD4+CTLA-4+T细胞显著增多,CD4+T细胞显著减少;胃癌、结肠癌患者之间其外周血中CD4+CD25+FOXP3+Treg细胞、CD4+CD25+high Treg细胞、CD4+T细胞及CD4+CTLA-4+T细胞无显著差异。结论:胃肠道癌肿患者外周血CD4+CD25+FOXP3+Treg细胞显著高于健康献血者,这可能与胃肠道癌肿患者的免疫抑制和肿瘤的进展相关。

  16. Expressions of CD4 + CD25high regulatory T cells, TGF-β1 and COX-2 in the peripheral blood of prostate cancer patients%前列腺癌患者外周血中CD4+CD25high调节性T细胞及调节因子TGF-31和COX-2的表达

    Institute of Scientific and Technical Information of China (English)

    夏桃林; 刘涛; 吴振权; 张海滨; 杨明; 刘绍远; 何灼彬; 李辽源

    2011-01-01

    Objective: To investigate the expressions of CD4+ CD25high regulatory T cells, TGF-β1 and COX-2 in the periphe-ral blood of prostate cancer (Pca) patients, and analyze the role of CD4+ CD25high regulatory T cells in the pathogenesis of Pca and their relationship with TGF-pl and COX-2. Methods: We used flow cytometry to calculate the percentage of CD4+ CD25high regulatory T cells in the CD4 + T cells in the peripheral blood mononuelear cells ( PBMC) from 30 Pca patients (11 localized and 19 non-localized cases) and 20 healthy volunteer controls, determined the expressions of TGF-pl and COX-2 in the serum by ELISA, and analyzed their correlation with the CD4+ CD25high regulatory T cells in the Pca patients as well as the differences between the localized and non- localized cases. Results: CD4+ CD25high regulatory T cells accounted for (18.32 ±7.49) % in the CD4+ T cells in PBMCs from the Pca patients, significantly higher than (7.77 ±1.86) % from the controls (P 0.05 ). The expressions of TGF-pl and COX-2 in the peripheral blood were (215.97 ±55.16) ng/ml and (6.88 ±5.14) ng/ml in the Pca patients, in comparison with (149.75 ±47.11) ng/ml (P 0.05 ) in the controls. Multiple linear regression analysis showed no significant correlation between the expression of CD4 + CD25high regulatory T cells in PBMCs and those of TGF-pl and COX-2 in the peripheral blood of the Pca patients. There were no significant differences between the localized and non-localized Pca groups in the expressions of CD4 + CD25high regulatory T cells, TGF-pl and COX-2 (P > 0.05). Conclusion-. CD4 + CD25high regulatory T cells in in PBMCs are involved in the pathogenesis of Pca. The proliferation of CD4 + CD25 high regulatory T cells is not significantly correlated to the expressions of TGF-pl and COX-2 in the peripheral blood, but maybe to the tumor itself and the local tumor microenvironment.%目的:通过检测前列腺癌患者以及健康志愿者外周血中CD4+ CD25high

  17. 抗ICOS抗体体外对哮喘大鼠血液和淋巴液CD4+CD25+Foxp3+调节性T细胞数量及其功能影响%Influence of anti-ICOS antibody on quantity and function of CD4 + CD25 + Foxp3 + Treg from lymph and blood of rats with bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    赵磊; 冯学斌; 王跃嗣; 崔晴晴; 曹茵茵

    2012-01-01

    AIM: To investigate the influences of anti-ICOS antibody (anti-ICOSAb) on quantity and function of CD4+ CD25+ Foxp3+ Treg cells from lymph and peripheral blood of rats with bronchial asthma. METHODS: The mononuclear cells ( MNC) from lymph and blood were co-cultured with anti-ICOSAb, and then the percentage of CD4+ CD25+ Foxp3+ Treg cells were analyzed by flow cytometer (FCM) and the levels of IL-10 and TGF-pi in supernatants were determined by ELISA. RESULTS; The MNC were collected from lymph and blood at 0, 24 and 48 h after the last challenge, respectively, and the cells were cultured for 96 h in vitro. The percentage of CD4+ CD25 + Foxp3+ Treg cells in the MNC from lymph was significantly higher than that from blood in each group (P < 0.05); The percentage of CD4 + CD25 Foxp3+ Treg cells in the MNC from lymph and blood in asthma group was significantly lower compare with the normal control group (P < 0.05); The percentage of CD4+ CD25 + Foxp3+ Treg cells in the MNC from lymph and blood in the anti-ICOSAb group obviously decreased compare with the asthma group ( P < 0. 05). At 0 h after the last challenge, the level of IL-10 in the supernatant of MNC from lymph and blood in the anti-ICOSAb group were significantly lower than that of the control and asthma groups (P < 0. 05), while there were no significant differences of TGF-pi expression in the supernatant of MNC from lymph and blood in each group at different time points. CON-CLUSION: Blocking the ICOS/ICOSL signaling pathway by anti-ICOSAb could exacerbate the deficiency of CRT CD25+ Foxp3+Treg cells from lymph and Wood in bronchial asthmatic rat, meanwhile inhibit the CD4 + CD25 + Foxp3+Treg cells secreting IL-10 at 0 h after the last challenge, but have no significant effect on the secretion of TGF-β1.%目的:研究抗ICOS抗体对哮喘大鼠外周血和淋巴液来源CD4+ CD25+ Foxp3+调节性T细胞(Treg)数量及其功能的影响.方法:抗ICOS抗体处理血液和淋巴液中单个核细胞(MNC

  18. Different Responses of CD4+CD25+ Regulatory T Cells in Allergic Asthma Patients and Asymptomatic Sensitised People After Stimulation with Allergen in Vitro%CD4+CD25+调节性T细胞在过敏性哮喘和无症状的过敏者中表达的差异

    Institute of Scientific and Technical Information of China (English)

    王丽慧; 杨炯; 杨亦斌

    2011-01-01

    目的:比较过敏性哮喘患者、无症状的过敏者和不过敏的健康人外周血CD4+CD25+调节性T细胞(Treg)数量的差异及对特异性过敏原刺激的反应.方法:选取急性发作期的尘螨过敏性哮喘患者20例,无症状的尘螨过敏者24例,不过敏的健康人22例,分离外周血单个核细胞(PBMC)并进行CFSE染色,分别在不刺激和1mg/L尘螨抗原(rDer p 1)刺激情况下体外培养7 d,流式细胞仪检测CD4+CD25+Treg的比率和分裂指数;ELISA法检测各组细胞培养上清液和血清中白细胞介素-4(IL-4)和干扰素-γ(IFN-γ)的水平.结果:过敏性哮喘患者CD4+CD25+Treg比率和IFN-γ基础水平均低于无症状的尘螨过敏者和不过敏的健康人,且过敏原刺激后增加不明显;但IL-4的基础水平最高,过敏原刺激后差异更显著.无论刺激与否,无症状的尘螨过敏者CD4+CD25+Treg比率均与不过敏的健康人的水平接近.但过敏原刺激后无症状的尘螨过敏者CD4+CD25+Treg比率高于过敏性哮喘患者,且存在高水平的IFN-γ反应.结论:接触过敏原后,过敏性哮喘患者和无症状的过敏者表现出不同的免疫反应模式.过敏性哮喘患者抗原特异性CD4+CD25+Treg反应不足,存在过高Th2反应.无症状过敏的发生可能与机体对特异性过敏原刺激产生高水平的CD4+CD25+Treg反应及高水平的IFN-γ反应有关.%Objective: To determine whether there are differences in the numbers and the responses of CD4+CD25+ regulatory T cells (Treg) in allergic asthmatics and people asymtomatic sensitised to specific allergen after specific allergen exposure. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 20 patients sensitized to house dust mite with asthma, 24 asymptomatic subjects sensitized to house dust mite, and 22 non-allergic subjects. Cells were cultured without stimulation and with 1 mg/L antigen of dust mite rDer p 1. Frequencies and division index of CD4+ CD25+ Tregs were

  19. The investigation of expression level of TSLP in thymus and the phenotype of CD4+CD25+Foxp3+ Treg cells in patients with myasthenia gravis%重症肌无力胸腺基质淋巴细胞生成素表达与CD4+CD25+Foxp3+Treg细胞表型的研究

    Institute of Scientific and Technical Information of China (English)

    孙延鹏; 卢祖能; 孙强; 杨超; 王云甫

    2012-01-01

    Objective To investigate the correlation between expression level of thymic stromal lymphopoietin (TSLP) in thymus and the expression of CD4+ CD25+ Foxp3+ Treg cells in patients with myasthenia gravis (MG). Methods The ratio of CD4+ CD25+ Foxp3+ Treg/CD4+ T cell were tested by flow cytometry from peripheral blood mononuclear cell which has been dealt with CD4+CD25+ antibody on the surface of the cell and Foxp3+ antibody into the cell in 16 patients with MG and 23 patients with congenital heart disease (control group). At the same time, thymuses cut from the corresponding patients were obtained to count the amount of TSLP positive Hassell corpuscles, the amount of TSLP positive Hassell corpuscles was compared between the two groups. The correlation between the amount of TSLP positive Hassall's corpuscles and CD4+ CD25+ Foxp3+ Treg cells expression was analyzed by logistic regression test. Results There was no statistical difference of the ratio of CD4+ CD25+ T/CD4+ T cells between the MG group [ (6. 24 + 0. 62) %] and the control group [ (6. 56 ±0. 65) %] (P>0. 05), but the ratio of CD4+ CD25+ Foxp3+ Treg/CD4+ T cells in MG group [ (6. 24 ± 0. 62)%] was significantly lower than that in the control group [ (5. 73 ±0. 56)%] (F<0. 01). The number of TSLP positive Hassell corpuscles in MG group was significantly fewer than that in the control group (6. 81 + 2. 17 versus 18. 87 + 3. 06, P<0. 01). The logistic regression analysis demonstrated that the expression of TSLP in the MG groups was linear related with the expression of Treg cells (R2 =0. 158, F= 13. 42, P< 0. 01). Conclusions The inadequate expression of TSLP is positively related to phenotype defiiency of the CD4+ CD25+Foxp3+ during Treg cell growth.%目的 探索重症肌无力患者胸腺基质淋巴细胞生成素(TSLP)表达水平与CD4+CD25+Foxp3+调节性T细胞(Treg)表型的相关性.方法 MG组(16例经胸腺切除的MG患者)及对照组(23例先天性心脏病心脏手术后患者)取

  20. Analysis on CD4 + CD25 + T cell in HCV infection and HCV/HIV co-infection%HCV感染者和HCV/HIV合并感染者免疫调节

    Institute of Scientific and Technical Information of China (English)

    康辉; 尚红; 刁莹莹; 范霞; 代娣; 姜桐军; 耿文清

    2005-01-01

    目的探讨我国单纯丙型肝炎病毒(HCV)感染者和HCV/HIV合并感染者免疫应答的相关机制.方法分离人外周血单个核细胞;流式细胞仪(FACS)检测CD4+T细胞和CD4+CD25+T细胞表达水平.结果CD4+CD25+T细胞占外周血单个核细胞中CD4+T细胞比例(%CD4+CD25+),HCV感染组明显高于健康对照组(19.2%>13.8%,P<0.05),HCV/HIV合并感染组明显低于对照组(6.9%<13.8%,P<0.001),更明显低于HCV感染组(P<0.001).结论HCV感染者体内CD4+CD25+T细胞增殖明显,提示CD4+CD25+T细胞在HCV慢性感染中发挥免疫调节作用.HCV/HIV合并感染时,CD4+CD25+T细胞受损,从而影响免疫调节功能.

  1. 初发Graves病患者CD4~+CD25~+Foxp3~+调节性T细胞水平的研究%Study on the Frequencies of CD4~+CD25~+Foxp3~+Regulatory T Cells in the Patients with Graves' Disease

    Institute of Scientific and Technical Information of China (English)

    高桂华; 赵连爽

    2010-01-01

    采用胞内染色技术分别检测45例初发Graves病患者(GD组)和20例健康成人(对照组)CD4~+CD25~+Foxp3~+调节性T细胞水平的变化,并用放射免疫分析法检测TT3、TT4和TSH.结果 显示GD组TT3和TT4水平高于对照组,而TSH水平低于对照组.认为初发GD患者CD4~+CD25~+Forxp3~+调节性T细胞水平明显下降,低于正常人水平,在GD的发病中可能发挥重要作用.

  2. Impact of the CD4 + CD25nt/hiCD127loregulatory T cells on the immune status and disease progression in HIV-1 infected individuals%CD4+CD25 nt/hi CD127lo调节性T细胞对HIV感染者免疫状态及病程进展的影响

    Institute of Scientific and Technical Information of China (English)

    周明奎; 薛以乐; 宫菊丽; 周磊明; 郑晓虹; 盖晶; 沈方伟; 张玮; 宁镇; 岳清; 卢伟; 潘启超; 康来仪; 钟平; 朱文斯; 王盈

    2007-01-01

    目的:探讨具有CD4+CD25nt/hi CD127lo特征的调节性T细胞频率对中国HIV-1感染者免疫状态及病程进展的影响.方法:选取100名未经治疗的HIV-1感染者和4个年龄组的312名健康人对照,采集静脉血,经三重免疫荧光染色,用流式细胞术分析CD4+CD25+Treg表型和CD4+CD25nt/hiCD127loTreg频率并进行CD4+T细胞绝对计数;应用酶联免疫斑点技术(ELISpot)在单细胞水平观察受试者的HIV-1特异性细胞免疫功能;平行检测HIV感染者的病毒载量(NASBA方法).结果:不同病程的HIV-1感染者外周血中CD4+CD25nt/hiCD127loTreg频率存在差异,进展期高于新近感染者(P<0.001),其平均水平显著高于健康人(P<0.001);CD4+CD25nt/hiCD127loTreg频率与HIV感染者CD4+T细胞数量呈显著负相关(r=0.354,P<0.01),与病毒载量呈明显正相关(r=0.287,P<0.01);高频率CD4+CD25nt/hiCD127loTreg HIV-1感染者(进展期)的外周血PBMCs经HIV-1多肽刺激后分泌IFN-γ的CD8+T细胞频率明显低于无症状的新近感染者.结论:初步证实HIV-1感染者外周血中CD4+CD25nt/hiCD127kloTreg细胞频率增加与CD4+T细胞数量降低及病程进展相关;高频率CD4+CD25nt/hiCD127lo Treg细胞对HIV-1感染者的细胞免疫功能具有抑制作用.本结果为进一步阐明HIV持续感染的免疫机制提供了新依据.

  3. Study on the correlation between CD4+CD25+Foxp3+T regulatory cells and NK cells in decidual tissues of patients with preeclampsia%子痫前期患者蜕膜中CD4+CD25+Foxp3+调节性T细胞及NK细胞的相关研究

    Institute of Scientific and Technical Information of China (English)

    王莲莲; 蒋宏颉; 魏军

    2011-01-01

    Objective; To study the correlation between CD4 + CD25 + Foxp3 + T regulatory cells and NK cells in decidual tissues of patients with preeclampsia, explore the related immune changes in pathogenesis of preeclampsia. Methods; 30 cases with preeclampsia (13 cases with mild preeclampsia and 17 cases with severe preeclampsia) and 30 normal pregnant women of late pregnancy were selected, lmmu-nohistochemical method was used to detect and calculate CD4 + CD25 + Foxp3 + T regulatory cells and NK cells in decidual tissues, the average gray value was also detected. Results: The positive expression rate of CD4 + CD25 + Foxp3 + T regulatory cells in decidual tissues in preeclampsia group was significantly lower than that in normal late pregnancy group ( P < 0. 05 ) . The amount of NK cells in decidual tissues in preeclampsia group was significantly higher than that in normal late pregnancy group (P < 0. 05 ) , the average gray value of CD56 immunohis-tochemical staining in NK cells was significantly higher than that in normal late pregnancy group (P < 0. 05) . Conclusion: The amount of CD4 + CDjj + Foxp3 * T regulatory cells in decidual tissues in patients with preeclampsia is significantly lower than that in normal pregnant women of late pregnancy; the amount of NK cells in decidual tissues in patients with preeclampsia is significantly higher than that in normal pregnant women of late pregnancy, which induces maternal - fetal immune unbalance and activity of NK cells, then the killing activity is enhanced, preeclampsia occurs.%目的:对子痫前期(PE)患者蜕膜中CD4+CD25+Foxp3+调节性T细胞(CD4+CD25+Foxp3+Treg)和NK细胞进行相关研究,探讨子痫前期发病机制中相关的免疫学变化.方法:选择子痫前期患者30例(轻度13例、重度17例)、正常晚期妊娠妇女30例.采用免疫组织化学法检测胎盘蜕膜CD4+CD25+Foxp3+调节性T细胞和NK细胞后计数并检测其平均灰度值.结果:1.子痛前期患者蜕膜CD4+CD25+Foxp3+Treg

  4. Differences of CD4+CD25+ regulatory T cells between food allergy mice and normal mice%食物过敏与正常小鼠CD4+CD25+调节性T细胞的差异性研究

    Institute of Scientific and Technical Information of China (English)

    程茜; 陈玉梅

    2013-01-01

    Objective:To compare the quantities and functions of CD4+CD25+ regulatory T(Treg)cells between food allergy mice model and normal mice model. Methods: SPF Balb/c female mice of 4-6 weeks on egg-free diet were randomly divided into ovalbumin (OVA) group(n=8) and normal control group(n=8). Quantitative changes of CD4+CD25+ Treg cells in the spleen mononuclear cell suspension were analyzed by flow cytometry. Levels of serum interleukin-lO(IL-lO) and transforming growth factor-β1(TGF-βl) in OVA mice and normal control mice were detected by enzyme-linked immunosorbent assay (ELISA). Results: Percentage of CD4+ CD25+ Treg cells in OVA group was lower than that in normal control group (P<0.05 ), and percentage of forkhead transcription factor3+(Foxp3 + )CD4+CD25 + Treg cells in OVA group was significantly lower in OVA group than in normal control group(P<0.01). Levels of IL-10 and TGF-β1 were lower in OVA group than in normal control group(P<0.05)(P<0.01). Conclusions:There are differences in quantities and functions of Treg cells between food allergy and normal mice.%目的:比较食物过敏(food allergy,FA)小鼠与正常小鼠模型CD4+CD25+调节性T(regulatory T,Treg)细胞数量及功能差异.方法:4~6周龄SPF级无鸡蛋喂养Balb/c雌鼠随机分为2组,每组8只.分别为卵清蛋白(ovalbumin,OVA)致敏组和正常对照组.采用流式细胞术分析其脾脏单个核细胞悬液中CD4+CD25+ Treg细胞的数量变化;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测OVA致敏组与正常对照组血清白介素10(interleukin-10,IL-10)和转化生长因子-β1 (transforming growth factor-β1,TGF-β1)水平.结果:OVA组CD4+CD25+T淋巴细胞的百分比低于正常对照组(P<0.05),并且叉状头转录因子3阳性(forkhead transcription factor3+,Foxp3+)CD4+CD25+Treg细胞的百分比显著低于正常对照组(P<0.01);OVA组IL-10低于正常对照组(P<0.05),TGF-β1水平显著低于正常对照组(P<0.01).结论:FA

  5. 支气管哮喘患儿CD4+ CD25+ Foxp3+ IL-10+ T淋巴细胞水平变化和意义%Changes and significances of CD4 + CD25 + FOXP3 + IL-10 + T cells in children with asthma

    Institute of Scientific and Technical Information of China (English)

    王炜; 李芳; 段国威; 吴晓玲; 宋青

    2013-01-01

    目的:探讨对尘螨过敏的轻度持续支气管哮喘患儿淋巴细胞增殖情况及CD4+ CD25+ Foxp3+ IL-10+T淋巴细胞水平变化.方法:选择30例对尘螨过敏的轻度持续支气管哮喘患儿作为实验组,同时选择30例健康儿童作为对照组.分离所有入选者的外周血淋巴细胞,给予户尘螨浸出液刺激48 h后检测淋巴细胞增殖的刺激指数以及CD4+ CD25+ Foxp3+ IL-10+T淋巴细胞水平变化.结果:支气管哮喘患儿外周血淋巴细胞接受户尘螨浸出液刺激后淋巴细胞增殖的刺激指数显著高于对照组(P<0.01),支气管哮喘患儿CD4+ CD25+ Foxp3+ IL-10+T淋巴细胞水平显著低于对照组(P<0.01).结论:支气管哮喘患儿接受过敏原刺激后发生明显的增殖反应,支气管哮喘患儿存在CD4+ CD25+ Foxp3+ IL-10+T淋巴细胞功能障碍.%Objective: To explore the proliferation of T lymphocytes and the changes of CD4 + CD25 + Foxp3+ IL - 10 + T lymphocytes in children allergic to house dust mite with mild persistent asthma. Methods: Thirty children allergic to house dust mite ( HDM) with mild persistent asthma were selected as experimental group and 30 healthy children were selected as control group. Peripheral blood mononu-clear cells (PBMCs) were isolated from the subjects. After 48 hours of in vitro stimulation with HDM extracts, the stimulation indexes (SI) of lymphocytes and the changes of CD4 + CD25 + Foxp3+ IL - 10+ T lymphocytes were measured by flow cytometry. Results: SI of lymphocytes increased significantly in asthma group compared with control group, there was statistically significant difference ( P < 0. 001) . The level of CD4+ CD25+ Foxp3+ IL — 10+ T lymphocytes in asthma group was statistically significantly lower than that in control group (P < 0.01) . Conclusion: T lymphocyte proliferation obviously can be observed in asthmatic children when they were stimulated by ,HDM extract. There is functional insufficiency of CD4+ CD25+ Foxp3+ IL - 10+ T

  6. The Prospects of the usage of CD+4CD+25 regulatory T cells in cancer immunotherapy%CD+4CD+25调节性T细胞在肿瘤免疫治疗中的价值及应用前景

    Institute of Scientific and Technical Information of China (English)

    付泽娴; 蔡建辉

    2005-01-01

    恶性肿瘤的临床治疗主要是手术治疗、化学治疗和放射治疗.近年来,随着分子生物技术的不断发展,肿瘤的生物治疗在临床应用中的地位日渐突出.但是免疫细胞过继治疗作用的一过性和功能抑制成为影响其临床应用的瓶颈,其中CD+4CD+25调节性T细胞(CD+4CD+25 regulatory T cell ,Treg)在抑制肿瘤免疫方面起着重要作用.本文就其近年来的肿瘤临床研究进展做一综述.

  7. Detection of interleukin-10 and transforming growth factor-β1 in the culture supernatant of CD4+CD25+ T cells from patients with alopecia areata%斑秃患者外周血CD4+CD25+T细胞培养上清液白介素10和转化生长因子β1检测

    Institute of Scientific and Technical Information of China (English)

    马新华; 邵文俊; 金宛宛; 高宇

    2014-01-01

    Objective To evaluate the potential association of CD4+CD25+ T cells with alopecia areata.Methods Totally,this study enrolled 23 patients with progressive alopecia areata,25 patients with stable alopecia areata,and 25 healthy controls.Peripheral blood was isolated from these subjects followed by isolation of CD4+ CD25+ regulatory T cells,which were then cuhured with the presence of anti-CD3 and-CD28 monoclonal antibodies for four days.Subsequently,enzyme-linked immunosorbent assay was performed to measure the levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 in the culture supematant of these T cells.Results The levels of IL-10 and TGF-β1 were (31.68 ± 6.78) pg/ml and (32.29 ± 6.8) pg/ml respectively in the culture supernatant of CD4+CD25+ regulatory T cells from patients with progressive alopecia areata,significantly lower than those from the healthy controls ((57.34 ± 14.15) pg/ml and (57.43 ± 15.16) pg/ml,both P < 0.05) and patients with stable alopecia areata ((52.56 ± 13.02) pg/ml and (61.75 ± 14.10) pg/ml,both P < 0.05).However,no significant difference was observed in the supernatant levels of IL-10 or TGF-β1 between the healthy controls and patients with stable alopecia areata.Conclusions The secretion of IL-10 and TGF-β1 by CD4+CD25+ T cells is decreased in patients with progressive alopecia areata,which may contribute to the pathogenesis of alopecia areata.%目的 探讨CD4+CD25+T细胞与斑秃发病之间的关系.方法 收集了3组研究对象,其中健康对照组25例、稳定期斑秃患者25例、进展期斑秃患者23例.抽取所有对象外周血,提取CD4+CD25+T细胞,培养4d,收集培养上清液,ELISA法检测上清液IL-10和TGF-β1水平.结果 进展期斑秃患者外周血CD4+CD25+T细胞培养的IL-10和TGF-β1分别为(31.68±6.78) pg/ml和(32.29±6.80) pg/ml,明显低于健康对照组(57.34±14.15) pg/ml、(57.43±15.16) pg/ml和稳定期斑秃患者(52.56±13.02) pg/ml和(61.75±14.10) pg

  8. CXC chemokine receptor 3 expression increases the disease-inducing potential of CD4+ CD25- T cells in adoptive transfer colitis

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Gad, Monika; Thomsen, Allan Randrup;

    2006-01-01

    of enteroantigen specificity; we also tested the enteroantigen-specific proliferative ability of CD4CD25 T cells from CXCR3 mice in vitro and found that they respond even more strongly than wild-type cells. CONCLUSIONS: The present data indicate that CXCR3 plays an important role in controlling the migration......-inflammatory therapy in inflammatory bowel disease. In this study, we have investigated the role of the chemokine receptor CXCR3 in the development of chronic colitis in a murine model. METHOD: Expression of CXCR3 on CD4 T cell from normal and colitic mice was assessed by flow cytometry. Development of colitis...... was followed after transfer of either normal or CXCR3CD4CD25T cell into immunodeficient host. In addition, the ability of regulatory T cell to function in vivo in the absence of CXCR3 was tested. RESULTS: We find CXCR3 to be expressed on 80% to 90% of CD4 T cells isolated from colitic mice compared with only 4...

  9. CD25 signaling regulates the function and stability of peripheral Foxp3+ regulatory T cells derived from the spleen and lymph nodes of mice.

    Science.gov (United States)

    Wang, Kunpeng; Gu, Jian; Ni, Xuhao; Ding, Zheng; Wang, Qi; Zhou, Haoming; Zheng, SongGuo; Li, Bin; Lu, Ling

    2016-08-01

    Regulatory T cells (Tregs) play a critical role in sustaining immune tolerance and maintaining immune balance to alloantigen after transplatation. However, the functions of peripheral Tregs in different organs have not been fully characterized. Here, we showed that spleen-derived Tregs exhibited higher expression of Foxp3, greater suppressive capacity, and lower levels of IL-17A secretion than lymph node-derived Tregs in vitro in the presence or absence of inflammatory cytokines, such as IL-6. We found a higher percentage of CD25(bright) Tregs among spleen-derived Tregs than among lymph node-derived Tregs. Additionally, in vivo experiments demonstrated that adoptive transfer of spleen-derived Tregs, but not lymph node-derived Tregs, alleviated ischemia-reperfusion injury. These results reveal novel functions of Tregs derived from peripheral organs. In particular, spleen-derived Tregs, primarily consisting of CD25(bright) cells, may provide a more significant contribution to the suppression of immune-mediated autoimmune and inflammatory disease. PMID:27344615

  10. 变应性鼻炎患者外周血CD4+CD25+Treg及Foxp3的检测及意义

    Institute of Scientific and Technical Information of China (English)

    王淑慧; 王桂琴

    2012-01-01

    目的 通过检测变应性鼻炎(AR)患者外周血中调节性T细胞(Treg)的含量,并与正常健康人外周血中Treg含量作比较,探讨Treg在AR患者发病过程中的作用机制.方法 30例AR患者为试验组(8周未用抗组胺、糖皮质激素),15例正常健康人为对照组,采用流式细胞术分别检测以上受试对象外周血中Treg的含量,结果以CD4+CD25+Treg、CD4+CD25highTreg及Foxp3占外周血T细胞的百分比表示.结果 AR患者外周血Treg含量明显低于正常人( P<0.05).结论 AR患者外周血Treg细胞比例明显减少,是变应性鼻炎的发病机制之一.

  11. LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

    Directory of Open Access Journals (Sweden)

    Lorenzo Islas-Vazquez

    2015-01-01

    Full Text Available Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells.

  12. Change and its significance of CD4+ CD25+ regulatory T cells in experimental murine mammary carcinoma model%小鼠乳腺癌实验动物模型中CD4+CD25+调节性T细胞的变化及意义

    Institute of Scientific and Technical Information of China (English)

    徐林; 蒋正刚; 李宝华; 熊思东

    2006-01-01

    目的 研究CD4+CD25+调节性T细胞在小鼠乳腺癌实验动物模型中的变化,并探讨其意义.方法 以4T1接种BALB/c小鼠建立小鼠乳腺癌动物模型;分别以接种后1周和4周为荷瘤早、晚期;用流式细胞术(FACS)检测小鼠CD4+CD25+Foxp3+调节性T细胞在肿瘤局部及引流淋巴结中的比例变化;通过特异性增殖和杀伤实验观察早、晚期肿瘤局部的免疫应答.结果 CD4+CD25+调节性T细胞在肿瘤浸润淋巴细胞中的比例晚期为7.36%±0.26%,高于早期4.47%±0.88%(P<0.05);在引流淋巴结中比例变化不大;肿瘤浸润淋巴细胞的抗原特异性增殖和杀伤能力明显减弱(P<0.05).结论 CD4+CD25+调节性T细胞在肿瘤局部存在富集,这可能是导致肿瘤局部免疫反应减弱的重要原因.

  13. An atopy-associated polymorphism in the ectodomain of the IL-4R(alpha) chain (V50) regulates the persistence of STAT6 phosphorylation.

    Science.gov (United States)

    Ford, Andrew Q; Heller, Nicola M; Stephenson, Linda; Boothby, Mark R; Keegan, Achsah D

    2009-08-01

    Several commonly occurring polymorphisms in the IL-4R(alpha) have been associated with atopy in humans; the Q576R and the S503P polymorphisms reside in the cytoplasmic domain, whereas the I50 to V50 polymorphism resides in the extracellular domain of the IL-4R(alpha). The effects of these polymorphisms on signaling remain controversial. To determine the effect of the polymorphisms on IL-4 signaling in human cells, we stably transfected the human monocytic cell line U937 with murine IL-4R(alpha) cDNA bearing the I or V at position 50 and the P503/R576 double mutant. Each form of the murine IL-4R(alpha) mediated tyrosine phosphorylation of STAT6 in response to murine IL-4 treatment similar to the induction of tyrosine phosphorylation by human IL-4 signaling through the endogenous human IL-4R(alpha). After IL-4 removal, tyrosine-phosphorylated STAT6 rapidly decayed in cells expressing I50 or P503R576 murine IL-4Ralpha. In contrast, STAT6 remained significantly phosphorylated for several hours after murine IL-4 withdrawal in cells expressing the V50 polymorphism. This persistence in tyrosine-phosphorylated STAT6 was associated with persistence in CIS mRNA expression. Blocking IL-4 signaling during the decay phase using the JAK inhibitor AG490 or the anti-IL-4R(alpha) Ab M1 abrogated the persistence of phosphorylated STAT6 observed in the V50-IL-4R(alpha)-expressing cells. These results indicate that the V50 polymorphism promotes sustained STAT6 phosphorylation and that this process is mediated by continued engagement of IL-4R(alpha), suggesting enhanced responses of V50 IL-4R when IL-4 is limiting.

  14. The expression of membrane interleukin-2 receptor(CD25) on the surface of peripheral blood mononuclear cells(PBMC) of pulmonary tuberculosis and its clinical significance%肺结核患者PBMC膜白介素-2受体(CD25)表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    王健; 李朝品; 刘智; 刘炳祥

    2003-01-01

    目的:探讨外周血单个核细胞(PBMC)膜白介素-2受体(CD25)表达在肺结核病鉴别诊断中的应用价值.方法:用生物素-链霉亲和素(BSA)法检测肺结核、支气管肺炎患者T细胞亚群及植物血凝素(PHA)诱导前后CD25表达水平.结果:支气管肺炎患者CD3+、CD4+、CD8+水平分别为(62.32±6.34)%、(47.52±7.16)%、(32.12±6.55)%,CD4+/CD8+ 比值为1.52±0.43,PHA诱导前后CD25水平分别为(4.56±1.52)%、(35.12±7.21)%.空洞型肺结核CD3+、CD4+、CD8+、CD4+/CD8+水平分别为(41.13±5.25)%、(43.38±5.15)%、(36.25±3.46)%和1.15±0.21,非空洞型肺结核CD3+、CD4+、CD8+、CD4+/CD8+水平分别为(46.29±5.60)%、(47.21±4.86)%、(32.36±4.03)%、1.46±0.25,相互比较CD3+、CD4+/CD8+差异均有显著性(P<0.01和P<0.05).空洞型肺结核与非空洞型肺结核患者PHA诱导前后CD25水平分别为(2.13±1.14)%、(27.25±3.50)%和(3.43±1.35)%、(31.14±4.11)%,两者相比差异均有显著性(P<0.01).结论:肺结核病患者体内存在明显的细胞免疫功能紊乱,主要表现为CD25表达水平降低,CD25表达水平与肺结核病的病情似有一定关系,其对肺结核病鉴别诊断具有重要价值.%Objective:To study the value of membrane interleukin-2 receptor(CD25) of peripheral blood mononuclear cells (PBMC) on the differential diagnosis of pulmonary tuberculosis. Methods:The expression of T cell subset and levels of CD25 before and after induction with PHA were detected by biotin-streptavidin(BSA) in patients with pulmonary tuberculosis and bronchopneumonia. Results:The levels of CD3+, CD4+, CD8+, CD4+/CD8+ and CD25 before and after induction in peripheral blood in patients with bronchopneumonia were(62.32±6.34)%,(47.52±7.16)%,(32.12±6.55)%, 1.52±0.43,(4.56±1.52)%,and (35.12±7.21)%,respectively. The levels in pulmonary tuberculosis with cavity were(41.13±5.25)%,(43.38±5.15)%,(36.25±3.46)%, 1.15±0.21,(2.13±1.14)%,and (27.25±3.50)% and in pulmonary tuberculosis

  15. HBV宫内感染新生儿外周血调节性T细胞表达%Detection and analysis of CD4 + CD25+ regulatory T cell in peripheral blood from newborns with HBV intrauterine infection

    Institute of Scientific and Technical Information of China (English)

    高怡; 郭健; 付振东; 郝海燕; 刘明慧; 汪波; 丰淑英; 王素萍

    2013-01-01

    目的 探讨CD4+ CD25+调节性T细胞(Treg)在乙肝病毒(HBV)宫内感染新生儿外周血中的表达和意义.方法 选择乙肝表面抗原(HBsAg)阳性孕妇及其分娩新生儿79例,用酶联免疫吸附试验检测孕妇和新生儿外周血HBV标志物,实时荧光定量PCR检测母亲和新生儿外周血HBV DNA含量,用流式细胞仪检测新生儿外周血CD4+ CD25+ Treg和CD4+ CD25+ Foxp3+ Treg水平.结果 宫内感染HBV新生儿外周血CD4+ CD25+Treg和CD4+ CD25+ Foxp3+ Treg占CD4+T细胞比例分别为(10.57±2.25)%和(1.67±0.37)%,均高于未感染新生儿,差异有统计学意义(P<0.05),随产妇HBV DNA载量增加,新生儿外周血CD4+ CD25+ Treg和CD4+CD25+ Foxp3+ Treg增加,CD4+ CD25+ Treg比例高于阴性组(P <0.05);CD4+CD25+ Treg和CD4+ CD25+Foxp3+ Treg均与产妇HBV DNA载量呈正相关(r=0.430、0.409,P<0.05).结论 Treg可能通过抑制机体细胞免疫反应影响乙肝病毒清除,新生儿HBV宫内感染可能与Treg表达上调有关.

  16. Two novel nonradioactive polymerase chain reaction-based assays of dried blood spots, genomic DNA, or whole cells for fast, reliable detection of Z and S mutations in the alpha 1-antitrypsin gene

    DEFF Research Database (Denmark)

    Andresen, B S; Knudsen, I; Jensen, P K;

    1992-01-01

    Two new nonradioactive polymerase chain reaction (PCR)-based assays for the Z and S mutations in the alpha 1-antitrypsin gene are presented. The assays take advantage of PCR-mediated mutagenesis, creating new diagnostic restriction enzyme sites for unambiguous discrimination between test samples...... from individuals who are normal, heterozygous, or homozygous for the mutations. We show that the two assays can be performed with purified genomic DNA as well as with boiled blood spots. The new assays were validated by parallel testing with a technique in which PCR is combined with allele...

  17. Effects of Points Transplantation on Allogeneic Cord Blood Stem Cell in Rheumatoid Arthritis in Peripheral Blood CD4+CD25+ Regulatory T Cells%异基因脐血干细胞穴位移植对类风湿关节炎大鼠外周血CD4+CD25+调节性T细胞的影响

    Institute of Scientific and Technical Information of China (English)

    姜兆荣; 高明利; 牛广华; 高玉杰; 刘东武

    2015-01-01

    目的:观察异基因脐血干细胞(hUCBSCs)穴位移植对类风湿关节炎大鼠外周血CD4+CD25+调节性T细胞(CD4+ CD25+ Treg)的干预作用及相关机制.方法:先进行脐血CD34+细胞分选,将100只大鼠随机分为正常对照组、模型组对照组、hUCBSC尾静脉注射治疗组、hUCBSCs外关穴注射治疗组、甲氨喋呤(MTX)灌胃治疗组,每组20只.采用邓安梅法建立胶原诱导性关节炎(CIA)大鼠模型.于大鼠免疫后第31天(除正常组及模型组用等体积蒸馏水)向外关穴、尾静脉注射0.5 mL氯化钠注射液和0.5mL hUCBSCs悬液(含干细胞2×107/mL),4周后采用流式细胞仪,对外周血CD4+ CD25+细胞的百分含量及其在CD4+T淋巴细胞中所占的比例进行检测.结果:hUCBSCs外关穴注射治疗组外周血CD4+ CD25+细胞的百分含量及其在CD4+T淋巴细胞中所占的比例与甲氨喋呤组比较明显增高,差异有统计学意义(P<0.01),hUCBSC尾静脉注射治疗组与甲氨喋呤组比较,无显著性差异(P>0.05).结论:hUCBSCs外关穴穴位注射治疗可能通过上调CD4+ CD25+调节性T细胞水平,抑制关节炎症和关节骨破坏吸收,有助于类风湿关节炎的治疗.

  18. Effect of Astragalus on CD4+ CD25+ T cells and cytokines in the mice model of asthma%黄芪对哮喘小鼠CD4+ CD25+调节性T细胞及IL-4IFN-γ IL-10的影响

    Institute of Scientific and Technical Information of China (English)

    刘瑞文; 李春霞; 李志华; 王郡甫

    2011-01-01

    目的 探讨黄芪对哮喘小鼠CD4+ CD25+调节性T细胞及Ⅱ-4、IFN-γ、IL-10的影响.方法 将BALB/c小鼠30只随机分为对照组、哮喘组和黄芪组.以卵蛋白(OVA)致敏激发法制备小鼠哮喘模型.酶联免疫吸附试验( ELISA)法检测支气管肺泡灌洗液(BALF)中IL-4、IFN-γ、IL-10及血清中IL-10的含量;流式细胞术(FCM)、反转录聚合酶链反应(RT-PCR)分别检测小鼠脾脏中CD4+ CD25+调节性T细胞数量及FoxP3mRNA表达情况.结果 哮喘组小鼠BALF中IL-4含量明显高于对照组(P<0.01)而低于黄芪组(P<0.01).与对照组相比,哮喘组小鼠BALF中IFN-γ、IL-10、血清中IL-10含量及脾脏中CD4+ CD25+调节性T细胞数量、FoxP3 mRNA表达水平明显降低(P<0.01);而黄芪组的上述改变较哮喘组显著增加(P<0.05).结论 CD4+ CD25+调节性T细胞参与了支气管哮喘的发病过程,黄芪可通过上调CD4+ CD25+调节性T细胞、FoxP3mRNA的表达及增加IL-10含量减轻哮喘炎症.

  19. A study of the effects of Schistosoma japonicum soluble egg antigen on CD4+CD25+regulatory T cells in patients with asthma%CD4+CD25+调节性T细胞在血吸虫可溶性虫卵抗原影响哮喘中的作用研究

    Institute of Scientific and Technical Information of China (English)

    朱云娟; 刘佩梅; 杨秀珍; 刘霞; 吴增强; 纪伟华; 安桂珍; 沈悦云; 刘金霞; 李健

    2011-01-01

    Objective To study the relationship between Schistosoma japonicum soluble egg antigen (SEA) and asthma and the effects of SEA on CD4+ CD25+ regulatory T cells (CD4+ CD25+ Treg) and expression of the Foxp3 gene. Methods BALB/C mice were each injected with 50 μg SEA peritoneally and through the foot pad once a week for 4 weeks. In the control group, all injections were with normal saline. Then asthma was induced with ovalbumin (OVA) in all mice. After mice were sacrificed, the lungs were subjected to pathologic examination; the bronchoalveolar lavage fluid (BALF) was collected and different cells were classified and counted after smearing and staining. Spleen cells were separated and the percentage of CD4+ CD25+ Treg out of total CD4+ T cells was determined using flow cytometry. Total spleen RNA was prepared and synthesized into cDNA through reverse transcription; cDNA was subjected to PCR amplification to determine the level of Foxp3 mRNA expression. Results Mild pulmonary inflammation was observed in the SEA immunization group, whereas severe inflammation was observed in the control group. Staining of the BALF revealed that the SEA immunization group had a much lower BALF cell density than did the control group. In the SEA immunization group, the percentage of eosinophils out of total cells was(2. 22± 1. 52)% while it was (19. 93±4. 08)% in the control group. The difference between the 2 groups was statistically significant (P<0. 05). Flow cytometry revealed that the percentage of CD4+ CD25+ Treg out of total CD4+ T cells was (32. 24±2. 19) % in the SEA immunization group while it was (27. 41±2. 87) % in the control group. The difference between the 2 groups was statistically significant (P<0. 05). The level of Foxp3 mRNA expression was higher than that in the control group as well. Conclusion SEA inhibits the development of asthma to some extent and it seems influence immune regulation through its effect on CD4+CD25+Treg.%目的 研究血吸虫可溶性虫

  20. 不同剂量粉尘螨提取液对哮喘小鼠CD4+CD25+调节性T细胞的影响%Effect of Dermatophagoides farinae extract at various dosages on CD4+CD25+ regulatory T cells of mice with asthma

    Institute of Scientific and Technical Information of China (English)

    吴雪郡; 黄英; 韩洁; 王模奎; 王莹; 王莉佳

    2012-01-01

    Objective To investigate the effect of Dermatophagoides farinae (Derf) extract at various dosages on CD4+CD25+ regulatory T cells (Tregs) of mice with asthma and optimize the maintenance dosage of the extract for immune therapy. Methods Mouse model of anaphylactic asthma was established by injecting i. p. CS7BL / 6 mice with the extract of Derf. Thirty-two model mice were divided into one control and three test groups. The mice in test groups 1, 2 and 3 were injected i. p. with Der f at low (100μg/ mouse), moderate (1 mg/mouse) and high (2 mg/mouse) dosages respectively, while those in control groups with physiological saline. The contents of CD4+CD25+ T cells and Foxp3+CD4+CD25+Tregs in splenocytes of mice were determined by flow cytometry, while the IL-10 and TGF-β1 levels in sera by ELISA. Results The percentages of CD4+CD25+T cells in CD4+T cells and the percentages of Foxp3+CD4+CD25+Tregs in CD4+CD25+ T cells as well as serum IL-10 and TGF-β1 levels were significantly lower in control group and test group 1 than in test groups 2 and 3 (each P 0. 05). Conclusion The optimal maintenance dosage of Der f extract for specific immune therapy of asthma in mice was 1 mg/ mouse.%目的 探讨不同剂量粉尘螨提取液对哮喘小鼠CD4+CD25调节性T细胞(Regulatory T cells,Tregs)的影响,确定粉尘螨提取液免疫治疗的最佳维持剂量.方法 用粉尘螨提取液经腹腔注射C57BL/6小鼠,建立过敏性哮喘模型,将32只哮喘小鼠随机分为4组:生理盐水组以及粉尘螨低(100 μg/只)、中(1 mg/只)和高(2 mg/只)剂量组,治疗完成后,采用流式细胞术检测小鼠脾细胞中CD4+CD25+T细胞及Foxp3+C D4+C D25 +Tregs的含量,ELISA法检测小鼠血清中细胞因子IL-10、TGF-β1的水平.结果 生理盐水组、粉尘螨低剂量组小鼠脾细胞中CD4+CD25+T细胞占CD4+T细胞的百分比均明显低于粉尘螨中剂量组和高剂量组(P均<0.05),而中剂量组与高剂量组比

  1. Changes and clinical significance of CD4+CD25+Foxp3+ regulatory T cell and IL-10,TGF-β1 in steroid-resistant asthma patients of peripheral blood%激素抵抗性哮喘患者外周血CD4+CD25+Foxp3+调节性T细胞及IL-10、TGF-β1的变化及意义

    Institute of Scientific and Technical Information of China (English)

    钱一龙; 赵振中; 朱建俊; 谢中华; 王珠美

    2013-01-01

    目的 观察激素抵抗性哮喘(SRA)患者外周血CD4+CD25+Foxp3+调节性T细胞(Treg)及白介素10(IL-10)、转化生长因子β1(TGF-β1)的变化,分析其在SRA发病机制中的作用.方法 采用流式细胞术检测40例SRA患者(激素抵抗组)外周血单个核细胞CD4+CD25+Foxp3+ Treg数目,并计算CD4+CD25+Foxp3+ Treg占CD4+T淋巴细胞的百分比;酶联免疫吸附试验(ELISA)法检测其血清IL-10、TGF-β1水平,并与激素敏感性患者(激素敏感组,46例)及正常体检者(正常组,30例)进行对比.结果 激素抵抗组患者外周血CD4+CD25+Foxp3+Treg占CD4+T淋巴细胞的百分比、CD4+CD25+Foxp3+Treg绝对值及血清IL-10、TGF-β1水平均明显低于激素敏感组与正常组(P<0.01,P<0.05);激素敏感组患者外周血CD4+CD25+Foxp3+Treg占CD4+T淋巴细胞的百分比、CD4+CD25+Foxp3+Treg绝对值及血清TGF-β1水平明显低于正常组(P<0.01,P<0.05),血清IL-10无明显差异(P>0.05);CD4+CD25+Foxp3+Treg/CD4+T及CD4+CD25+Foxp3+Treg绝对数均与血清IL-10、TGF-β1水平呈明显正相关(P<0.01).结论 SRA患者外周血CD4+CD25+Foxp3+ Treg数目减少及IL-10、TGF-β1含量减低可能与SRA的发生、发展有关.

  2. Role of Foxp3 expression and CD+4CD+25 regulatory T cells on the pathogenesis of childhood asthma%Foxp3表达与CD+4CD+25调节性T细胞在儿童哮喘发病中的作用

    Institute of Scientific and Technical Information of China (English)

    罗征秀; 刘恩梅; 邓兵; 李欣; 陈坤华; 王莉佳; 黄英; 符州

    2006-01-01

    目的研究Foxp3基因表达与CD+4CD+25调节性T细胞在哮喘发病中的作用.方法以确诊哮喘的患儿为研究对象,急性发作期15例、缓解期15例,同期选10例正常儿童作对照,提取外周血单个核细胞(PBMC)进行CD4、CD25表面标志及血浆、培养上清液IL-4、IFN-γ、IL-10和TGF-β等细胞因子的ELISA检测,同时收集哮喘患儿和正常儿童的诱导痰,用RT-PCR方法检测PBMC及诱导痰中转录因子Foxp3-mRNA的表达.结果 PBMC CD+4CD+25T细胞百分率在哮喘急性发作期、缓解期分别为(10.1±2.1)%、(11.7±2.5)%,低于对照组的(15.5±2.7)%(P分别<0.01、<0.05);对照组PBMC在体外培养后CD+4CD+25细胞百分率显著升高,同培养前比较差异有统计学意义(P<0.01).PBMC Foxp3-mRNA表达水平(Foxp3/β-actin) 在哮喘急性发作期、缓解期分别为0.46±0.14 、0.50±0.19,低于对照组0.77±0.22,诱导痰Foxp3-mRNA表达水平哮喘患儿也低于对照组;PBMC在体外培养后对照组Foxp3-mRNA表达水平较培养前升高(P<0.05),而哮喘患儿培养前后Foxp3-mRNA表达水平无显著变化.血浆及培养上清液IFN-γ、TGF-β在哮喘急性发作期、缓解期低于对照组 (P<0.05),且IFN-γ、TGF-β与PBMC Foxp3-mRNA水平、CD+4CD+25细胞百分率呈正相关. 哮喘患儿血浆及培养上清液IL-4显著高于对照组,急性发作期血浆IL-10显著高于对照组,而缓解期与正常组无显著性差异;IL-4、IL-10与PBMC Foxp3-mRNA水平、CD+4CD+25细胞百分率无相关性.结论哮喘患儿的TGF-β分泌不足、Foxp3基因表达降低、CD+4CD+25调节性T细胞数量减少及分化发育障碍可能在儿童哮喘的发病中起重要作用.

  3. Expression of surface markers on peripheral CD4+CD25high T cells in patients with atopic asthma: role of inhaled corticosteroid

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background CD4+CD25+ regulatory T cells (Tregs) mediate immune suppression through cell-cell contact with surface molecules,particularly cytotoxic T lymphocyte-associated antigen 4 (CTLA-4),glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR),and transforming growth factor β(TGF-β),but little is known about the exact role of Tregs in the pathogenesis of asthma.This study sought to characterize the expression of surface markers on peripheral blood mononuclear cells-derived Tregs in patients with atopic asthma and healthy subjects,and to investigate the effect of inhaled corticosteroid on them.Methods The expression of surface molecules on CD4+CD25hign Tregs was detected by flow cytometry.The effect of inhaled corticosteroid on expression of the surface molecules on Tregs was determined in vivo and in vitro.Total serum immunoglobulin E (IgE) and high-sensitivity C-reactive protein were measured by enzyme linked immunosorbent assay and latex enhanced immunoturbidimetric assay,respectively.Results Equivalent numbers of peripheral Tregs were found in patients with atopic asthma (stable and acute) and healthy subjects.Tregs preferentially expressed CTLA-4, GITR,toll-like receptor 4 (TLR4),latency-associated peptide (LAP/TGF-β1),and forkhead box P3 (FOXP3).Patients with acute asthma had decreased numbers of CD4+CD25high LAP+ T cells compared to healthy subjects and stable asthmatics.Inhaled corticosteroid enhanced the percentage of Tregs expressing LAP in vivo and in vitro dose-dependently.Furthermore,the percentages of Tregs expressing LAP were negatively correlated with total serum IgE levels and severity of asthma,but positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma.Concluslons The results suggest that membrane-bound TGF-β1 is a potential candidate for predicting the severity of asthma,and may contribute to the sustained remission of asthma,Strategies targeting

  4. Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells

    Science.gov (United States)

    2012-01-01

    Background Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation. Methods Naïve CBA mice (H2k) underwent transplantation of a C57BL/6 (B6, H2b) heart and were exposed to one of three types of music--opera (La Traviata), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed. Results CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to

  5. Tim-3 mRNA Expression in Peripheral Blood Mononuclear Cells and Its Relationship with CD4+CD25+ Regulatory T Cells from Asthmatic Children%哮喘儿童外周血单个核细胞Tim-3mRNA的表达及其与CD4+CD25+调节性T细胞的关系

    Institute of Scientific and Technical Information of China (English)

    陆小霞

    2011-01-01

    目的 观察哮喘患儿外周血单个核细胞(PBMC)中Tim-3 mRNA的表达及其与CD4+CD25+调节性T细胞(Treg)的关系,探讨Tim-3在哮喘发生发展中的作用.方法 收集哮喘门诊或住院患儿73例,其中哮喘缓解期38例(缓解组),轻至中度急性发作期35例(发作组).利用RT-PCR检测哮喘患儿PBMC中Tim-3 mRNA的表达并做半定量分析,流式细胞术检测PBMC中的CD4+CD25+ Treg的水平(CD4+CD25+ Treg占CD4+T细胞的百分比).利用酶联免疫吸附试验(ELISA)检测血浆中白细胞介素6(IL-6)、转化生长因子β(TGF-β)的水平,并分析Tim-3 mRNA与CD4+CD25+ Treg、IL-6水平的相关性.结果 哮喘发作组PBMC中Tim-3 mRNA吸光度值为(0.86±0.17),与缓解组(0.39±0.11)和正常对照组(0.06±0.03)比较,差异具有统计学意义(均P<0.05),并且缓解组与正常对照组比较差异亦具有统计学意义(P<0.05).哮喘发作组外周血CD4+CD25+ Treg百分率为(8.35±1.67)%,与缓解组[(10.21±2.04)%]和正常对照组[(12.43±2.58)%]比较,差异均具有统计学意义(P<0.05),并且缓解组与正常对照组比较差异亦具有统计学意义(P<0.05);哮喘发作组血浆中IL-6水平为(78.35±14.59)pg/mL,与缓解组[(36.48±9.18)pg/mL]和正常对照组[(10.24±3.57)pg/mL]比较,差异均具有统计学意义(P<0.05),缓解组与正常对照组比较差异亦有统计学意义(P<0.05).3组血浆中TGF-β水平没有明显差异;哮喘发作组和缓解组PBMC中Tim-3 mRNA的表达水平与CD4+CD25+ Treg百分率均呈负相关(r=-0.81,-0.79,均P<0.05),与IL-6的水平呈正相关(r=0.87,0.83,均P<0.01).结论 哮喘患儿PBMC中Tim-3 mRNA表达增高参与哮喘的发生与发展,其机制可能与升高血浆IL-6,抑制CD4+CD25+ Treg的生成有关.%Objective To detect the expression of T cell immunoglobulin mucin 3 ( Tim-3)mRNA in pcripheral blood mono nuclear cells(PBMC)isolated from asthmatic children and analyze its rclationship with CD4+ CD25+ rcgulatory T cells

  6. Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4+CD25+ T cells in patients with active tuberculosis

    Science.gov (United States)

    Kong, Bin; Liu, Gan-Bin; Zhang, Jun-Ai; Fu, Xiao-Xia; Xiang, Wen-Yu; Gao, Yu-Chi; Lu, Yuan-Bin; Wu, Xian-Jing; Qiu, Feng; Wang, Wan-Dang; Yi, Lai-Long; Zhong, Ji-Xin; Chen, Zheng W; Xu, Jun-Fa

    2016-01-01

    Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4+ but not CD8+ T cells. Most p35+CD4+ T cells and EBI3+CD4+ T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB. PMID:27158354

  7. Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4(+)CD25(+) T cells in patients with active tuberculosis.

    Science.gov (United States)

    Kong, Bin; Liu, Gan-Bin; Zhang, Jun-Ai; Fu, Xiao-Xia; Xiang, Wen-Yu; Gao, Yu-Chi; Lu, Yuan-Bin; Wu, Xian-Jing; Qiu, Feng; Wang, Wan-Dang; Yi, Lai-Long; Zhong, Ji-Xin; Chen, Zheng W; Xu, Jun-Fa

    2016-01-01

    Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4(+) but not CD8(+) T cells. Most p35(+)CD4(+) T cells and EBI3(+)CD4(+) T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB.

  8. Dysregulation of CD4+CD25+CD127lowFOXP3+ regulatory T cells in HIV-infected pregnant women

    DEFF Research Database (Denmark)

    Kolte, Lilian; Gaardbo, Julie C; Karlsson, Ingrid;

    2010-01-01

    Pregnancy represents a major challenge to immunologic tolerance. How the fetal "semiallograft" evades maternal immune attack is unknown. Pregnancy success may involve alteration of both central (thymic) and peripheral tolerance mechanisms. HIV infection is characterized by CD4(+) T-cell depletion......, chronic immune activation, and altered lymphocyte subsets. We studied immunologic consequences of pregnancy in 20 HIV-infected women receiving highly active antiretroviral therapy (HAART), and for comparison in 16 HIV-negative women. Lymphocyte subsets, thymic output, and cytokine profiles were measured...... prospectively during pregnancy and postpartum. A significant expansion of CD4(+)CD25(+)CD127(low)FoxP3(+) regulatory T cells indicating alteration of peripheral tolerance was seen during second trimester, but only in HIV-negative women. HIV-infected women had lower CD4 counts, lower thymic output and Th-2...

  9. Dysregulation of CD4+CD25+CD127lowFOXP3+ regulatory T cells in HIV-infected pregnant women

    DEFF Research Database (Denmark)

    Kolte, Lilian; Gaardbo, Julie C; Karlsson, Ingrid;

    2010-01-01

    , chronic immune activation, and altered lymphocyte subsets. We studied immunologic consequences of pregnancy in 20 HIV-infected women receiving highly active antiretroviral therapy (HAART), and for comparison in 16 HIV-negative women. Lymphocyte subsets, thymic output, and cytokine profiles were measured...... prospectively during pregnancy and postpartum. A significant expansion of CD4(+)CD25(+)CD127(low)FoxP3(+) regulatory T cells indicating alteration of peripheral tolerance was seen during second trimester, but only in HIV-negative women. HIV-infected women had lower CD4 counts, lower thymic output and Th-2...... course of HIV infection. However, despite HAART during pregnancy, HIV-infected women display different immunologic profiles from HIV-negative women, which may have importance for the induction of fetal-maternal tolerance and in part explain the increased risk of abortion in HIV-infected women....

  10. FoxP3(+)CD4(+)CD25(+) T cells with regulatory properties can be cultured from colonic mucosa of patients with Crohn's disease

    DEFF Research Database (Denmark)

    Rømer, Johanne Lade

    2005-01-01

    /winged helix transcription factor FoxP3 is a master gene for T(reg) function and defects in the FoxP3 gene lead to a clinical picture similar to inflammatory bowel disease (IBD). Murine colitis can be cured by adoptive transfer of T(regs) and ex vivo-generated gut-specific T(regs) represent an attractive...... option for therapy in CD. Thus, defective T(regs) could contribute to the development of CD. We cultured biopsies of colonic mucosa in the presence of high concentrations of interleukin (IL)-2 and IL-4 to overcome the anergic nature of naturally occurring CD4(+)CD25(+) T(regs) in the mucosa. We...

  11. Interplay of T Helper 17 Cells with CD4+CD25high FOXP3+ Tregs in Regulation of Allergic Asthma in Pediatric Patients

    Directory of Open Access Journals (Sweden)

    Amit Agarwal

    2014-01-01

    Full Text Available Background. There is evidence that Tregs are important to prevent allergic diseases like asthma but limited literature exists on role of TH17 cells in allergic diseases. Methods. Fifty children with asthma and respiratory allergy (study group and twenty healthy children (control group were recruited in this study. Total IgE levels and pulmonary function tests were assessed. The expression of Tregs and cytokines was determined by flow cytometry. Results. The average level of total IgE in study group (316.8 ± 189.8 IU/mL was significantly higher than controls (50 ± 17.5 IU/mL, P<0.0001. The frequency of TH17 cells and culture supernatant level of IL-17 in study group (12.09 ± 8.67 pg/mL was significantly higher than control group (2.01 ± 1.27 pg/mL, P<0.001. Alternatively, the frequency of FOXP3 level was significantly lower in study group [(49.00 ± 13.47%] than in control group [(95.91 ± 2.63%] and CD4+CD25+FOXP3+ to CD4+CD25+ ratio was also significantly decreased in study group [(6.33 ± 2.18%] compared to control group [(38.61 ± 11.04%]. The total serum IgE level is negatively correlated with FOXP3 level (r=-0.5273, P<0.0001. The FOXP3 expression is negatively correlated with the IL-17 levels (r=-0.5631, P<0.0001 and IL-4 levels (r=-0.2836, P=0.0460. Conclusions. Imbalance in TH17/Tregs, elevated IL-17, and IL-4 response and downregulation of FOXP3 were associated with allergic asthma.

  12. Assessment of the frequency of regulatory T cells (CD4+CD25+CD127-) in children with hemophilia A: relation to factor VIII inhibitors and disease severity.

    Science.gov (United States)

    El-Asrar, Mohamed Abo; Hamed, Ahmed El-Saeed; Darwish, Yasser Wagih; Ismail, Eman Abdel Rahman; Ismail, Noha Ali

    2016-01-01

    A rapidly growing evidence showed that regulatory T cells (Tregs) play a crucial role in tolerance to coagulation factors and may be involved in the pathogenesis of inhibitor formation in patients with hemophilia. We determined the percentage of Tregs (CD4CD25CD127) in 45 children with hemophilia A compared with 45 healthy controls, and assessed their relation to the clinical characteristics of patients and factor VIII (FVIII) inhibitors. Patients were studied stressing on frequency of bleeding attacks, joint pain, history of viral hepatitis, and the received therapy (FVIII precipitate/cryotherapy). FVIII activity and FVIII inhibitors were assessed with flow cytometric analysis of CD4CD25CD127 Tregs. According to residual FVIII activity levels, 30 patients (66.7%) had mild/moderate hemophilia A, whereas 15 (33.3%) patients had severe hemophilia A. The frequency of Tregs was significantly lower among all patients with hemophilia A compared with controls (2.59 ± 1.1 versus 3.73 ± 1.12%; P = 0.002). Tregs were significantly decreased among patients with FVIII inhibitors compared with the inhibitor-negative group (P hemophilia A had lower Tregs levels than those without (P = 0.34 and P = 0.011, respectively). A significant positive correlation was found between the percentage of Tregs and FVIII among hemophilia A patients. ROC curve analysis revealed that the cut-off value of Tregs at 1.91% could differentiate patients with and without FVIII inhibitors, with a sensitivity of 100% and a specificity of 91.3%. We suggest that alteration in the frequency of Tregs in young patients with hemophilia A may contribute to inhibitor formation and disease severity.

  13. Murine CD4+CD25- cells activated in vitro with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis in vivo

    Directory of Open Access Journals (Sweden)

    Majowicz Anna

    2012-12-01

    Full Text Available Abstract Background Induced regulatory T (iTreg lymphocytes show promise for application in the treatment of allergic, autoimmune and inflammatory disorders. iTreg cells demonstrate advantages over natural Treg (nTreg cells in terms of increased number of starting population and greater potential to proliferate. Different activation methods to generate iTreg cells result in iTreg cells that are heterogeneous in phenotype and mechanisms of suppression. Therefore it is of interest to explore new techniques to generate iTreg cells and to determine their physiological relevance. Methods Using phorbol myristate acetate (PMA/ionomycin and anti-CD3 activation of CD4+CD25- cells we generated in vitro functional CD4+CD25+ iTreg (TregPMA cells. Functionality of the generated TregPMA cells was tested in vivo in a mouse model of inflammatory bowel disease (IBD - CD45RB transfer colitis model. Results TregPMA cells expressed regulatory markers and proved to ameliorate the disease phenotype in murine CD45RB transfer colitis model. The body weight loss and disease activity scores for TregPMA treated mice were reduced when compared to diseased control group. Histological assessment of colon sections confirmed amelioration of the disease phenotype. Additionally, cytokine analysis showed decreased levels of proinflammatory colonic and plasma IL-6, colonic IL-1 β and higher levels of colonic IL-17 when compared to diseased control group. Conclusions This study identifies a new method to generate in vitro iTreg cells (TregPMA cells which physiological efficacy has been demonstrated in vivo.

  14. Study on the relationship between regulatory T cell CD 4+ CD25+ and CD8+ CD28- in the peripheral blood between graves disease%外周血中 CD4+CD25+与 CD8+CD28-调节性 T 细胞与Graves 病的关系研究

    Institute of Scientific and Technical Information of China (English)

    韦巍; 林英辉; 黄小琪

    2015-01-01

    目的:分析Graves病(GD)患者外周血中CD4+ CD25+和CD8+ CD28-调节性 T (Tr)细胞的变化。方法选择该院内分泌科门诊或住院部43例GD患者为研究对象,其中内分泌科门诊确诊的19例GD患者为试验初发组。接受治疗且甲状腺功能恢复正常的24例GD患者为治疗缓解组;选择同期健康体检者20例为健康对照组。采用流式细胞术检测3组外周血中CD4+ CD25+和CD8+ CD28- T r细胞水平。结果试验初发组外周血CD4+CD25+ T r细胞水平为(4.56±4.14)%,明显低于健康对照组的(8.84±4.45)%,差异有统计学意义( P<0.05),CD8+CD28- T r细胞水平为(14.95±5.38)%,与健康对照组的(10.65±6.37)%比较,差异无统计学意义(P>0.05)。治疗缓解组外周血中CD4+CD25+ Tr细胞水平为(6.99±6.35)%,与健康对照组比较,差异无统计学意义( P>0.05),但其CD8+ CD28- T r细胞水平为(20.48±6.07)%,高于健康对照组,差异有统计学意义( P<0.05)。结论 CD4+CD25+ T r细胞水平可能与GD发病有关,CD8+CD28-T r细胞可能与GD病程发展有关。%Objective To analyze the changes of the levels of CD4+CD25+ and CD8+CD28- T cells in the pe‐ripheral blood in patients with graves disease(GD) .Methods A total of 43 patients with GD were selected as objects in this study ,19 cases who were diagnosis in outpatient department were selected into incipience group ,24 cases who were treated and the thyroid function return to normal status were selected into alleviation group ,meanwhile 20 healthy persons were recruited into control group .The levels of CD4+ CD25+ and CD8+ CD28- regulator T cells in the peripheral blood were detected by flow cytometry .Results The CD4+CD25+ regulatory T cell levels in incipience group were (4 .56 ± 4 .14)% ,which was significant lower than(8 .84 ± 4 .45)% in the

  15. 丹参注射液联合地塞米松对哮喘大鼠CD4+CD25+调节性T细胞的影响%Influence of danshen injection combined with dexamethasone on CD4+CD25+ regulatory T cells of asthmatic rats

    Institute of Scientific and Technical Information of China (English)

    薛克营; 程立; 王成国; 李威; 石明

    2008-01-01

    目的 探讨丹参注射液联合地塞米松(DXM)抑制哮喘气道炎症的免疫学机制.方法 50只Wistar大鼠随机分成正常对照(NC)组、哮喘组、丹参组、DXM组、联合用药组,计数支气管肺泡灌洗液(BALF)中细胞总数并分类,HE染色行肺组织病理学检查,流式细胞仪检测外周血单个核细胞(PBMCs)中CD4+CD25+调节性T细胞(CD4+CD25+Treg)比例,ELISA检测BALF中IL-4、IL-5含量.结果 与哮喘组比较,药物干预组细胞总数、中性粒细胞(Neu)、淋巴细胞(Lym)、嗜酸性粒细胞(Eos)百分率下降(P<0.05,P<0.01),联合用药组下降程度大于丹参组、DXM组(P<0.05).哮喘组呈显著炎症变化,丹参组呈中度炎症变化,DXM组呈轻度炎症变化,联合用药组无炎症改变.与哮喘组比较,药物干预组CD4+CD25+Treg/CD4+T升高(P<0.05),IL4、IL-5含量下降(P<0.05),联合用药组CD4+CD25+ Tree/CD4+T升高程度和IL-4、IL-5下降程度大于丹参组和DXM组(P<0.05).结论 丹参注射液具有抑制哮喘大鼠气道炎症的作用,和DXM联合应用后,抑制作用更加明显,该作用可能和促进CD4+CD25+Treg产生,进而抑制IL-4、IL-5产生,纠正Th1/Th2失衡,最终减轻气道炎症有关.%Objective To investigate the immunological mechanism of inhibitory effect of Danshen injection combined with dexamethasone(DXM) on asthmatic airway inflammation.Methods 50 Wistar rats were randomly divided into normal control(NC),asthma,Danshen,DXM and Danshen+DXM group.Cytology study of Bronchoalveolar lavage fluid(BALF) was conducted.Pathology of lung tissue was done through HE.Flow eytometry was used to detect CD4+CD25+ regulatory T Cells(CD4+CD25+ Treg) ratio in peripheral blood mononuclear cells(PBMCs).IL-4 and IL-5 levels in BALF were detected by ELISA.Results Total cells number,percentage of lymphocytes,neutrophils and eosinophils(Eos) in BALF of the three treated groups were lower than that in asthma group(P<0.05,P<0.01),particularly in Danshen+DXM group

  16. Changes of Th17 cells and CD4+CD25+ regulatory T cells in peripheral blood of asthmatic children and their relationship with the situation of asthma.%哮喘患儿外周血Th17细胞CD4+CD25+调节性细胞变化及其与病情相关分析

    Institute of Scientific and Technical Information of China (English)

    马秋莉; 彭韶; 梁鹏; 李会娟; 张曼

    2011-01-01

    Objective To observe the levels of Thl7 cells, CD4+CD25+ regulatory T cells in the asthmatic children and relationship between the two types of cells and children' s condition. Methods Flow cytometry was used to detect the percentages of the Thl7 cells and CD4+CD25+ regulatory T cells in the peripheral blood of acute asthma children (asthma group, n - 60) .alleviated period asthma children (n = 30) and healthy children (healthy control group, n = 30).Acute asthma children were divided into 3 groups: mild, moderate and severe asthmatic patients. Results Compared with the healthy control group (1.02% ± 0.28%) and alleviated period asthma children (1.65% ± 0.38%), the numbers of CD4+ cells (Thl7) expressing IL-17 in peripheral blood of acute asthma(2.24% ± 1.02%) were increased, and the differences were statistically significant (P<0.05). The levels of CD4+CD25+T cells in peripheral blood of acute asthma and alleviated period asthma children (5.37% ± 0.80% ; 6.05% ± 0.87%) were significantly lower than those of healthy children (7.11% ± 0.89%) (P < 0.05). Thl7 cells were positively correlated with the course of childhood asthma(r = 0.649, P < 0.05).CD4+CD25+ regulatory T cells were negatively correlated with the course of childhood asthma (r =-0.599, P < 0.05). Conclusion The immunization response of Thl7 cells in peripheral blood of asthmatic children is strengthened, but the immune function of CD4+CD25+regulatory T cells is decresed. The severity of asthma is closely related to the inbal-ance of Th71ATreg cellular immunity.%目的 探讨支气管哮喘患儿外周血中辅助T细胞(Th) 17细胞和CD4+ CD25+调节性T细胞(Treg)的变化与儿童哮喘病情的相关性.方法 收集2009年月5月至2010年4月于郑州大学第一附属医院就诊的患儿,均为首次确诊哮喘或规范吸入激素停用>3个月后复发及近1个月内无明显感染者.采用流式细胞仪测定患儿外周血中Th17细胞及CD4+CD25+Treg比例的变化.结果 Th

  17. Effect of Lactobacillussalivariuson the Number of CD4+CD25+Foxp3+Treg Cells and the Expression of TGF-β1 in Asthma Balb/c Mice%唾液乳杆菌对哮喘小鼠CD4+CD25+Foxp3+Treg细胞数量及TGF-β1表达的影响

    Institute of Scientific and Technical Information of China (English)

    相云; 尚云晓; 李淼

    2015-01-01

    Objective To explore the effect of Lactobacillussalivariuson the number of CD4+CD25+Foxp3+Treg cells and expression of transform⁃ing growth factorβ1(TGF⁃β1)in asthma Balb/c mice. Methods Thirty⁃two female Balb/c mice were randomly divided into four groups:the nor⁃mal control group,the asthma group,the Lactobacillus salivarius group,and the asthma combined Lactobacillussalivariusgroup. Acute asthma mod⁃el was established by the ovalbumin challenge method. After extraction of primary spleen cells,flow cytometry was used to test CD4+CD25+Foxp3+Treg/CD4+T ratio in spleen lymphocytes. The levels of IL⁃4,IFN⁃γand TGF⁃β1 in the spleen cell culture supernatant were measured by ELISA method. Results The level of Th2 cytokine(IL⁃4)in the spleen cell culture supernatant of the asthma group was significantly higher than that of the control group(P<0.05),however,the level of Th1 cytokine(IFN⁃γ)was significantly lower than that of the control group(P<0.05). The ex⁃pression level of Th2 cytokine(IL⁃4)in the Lactobacillussalivariusintervention group was significantly decreased compared with the asthma group, and the Th1 cytokine(IFN⁃γ)expression level was elevated compared with the asthma group(P<0.05). The level of TGF⁃β1 in the Lactobacillus salivarius intervention group was higher than in the asthma group(P<0.05). The proportion of CD4+CD25+Foxp3+Treg/CD4+T in spleen lympho⁃cytes in the asthma group was lower than that in the control group(P<0.05),and was higher in the Lactobacillus salivarius intervention group than in the asthma group(P<0.05). Conclusion CD4+CD25+Foxp3+Treg was associated with the pathogenesis of asthma. Lactobacillus salivarius could adjust Th1/Th2 imbalance and reduce asthma inflammation through up⁃regulation of CD4+CD25+Foxp3+Treg and TGF⁃β1 expression.%目的:探讨唾液乳杆菌对哮喘Balb/c小鼠CD4+CD25+Foxp3+Treg细胞数量及转化生长因子β1(TGF⁃β1)表达的影响。方法将32只

  18. TL1A increases expression of CD25, LFA-1, CD134 and CD154, and induces IL-22 and GM-CSF production from effector CD4 T-cells.

    Directory of Open Access Journals (Sweden)

    Kirsten Reichwald

    Full Text Available Elevated levels of the cytokine TL1A is associated with several autoimmune diseases e.g. rheumatoid arthritis and inflammatory bowel disease. However, the exact role of TL1A remains elusive. In this study, we investigated the function of TL1A in a pro-inflammatory setting. We show that TL1A together with IL-12, IL-15 and IL-18 increases expression of the co-stimulatory molecules CD154 (CD40 ligand and CD134 (OX40 on previously activated CD4+ T cells. This indicates that TL1A functions as a co-stimulatory molecule, decreasing the activation threshold of T-cells. We have previously shown that TL1A co-stimulation strongly induces IL-6 in human healthy leukocytes. Interestingly, the cytokine-activated effector T-cells did not produce IL-6 in response to TL1A, indicating distinct effects of TL1A on different cell populations. We further show that this co-stimulation increases the expression of CD25 (IL-2Rα and CD11a (α-chain of LFA-1 on CD4 T-cells, likely governing increased IL-2/IL-15 sensitivity and cell-cell contact. Along with this, TL1A co-stimulation caused a specific induction of IL-22 and GM-CSF from the activated T-cells. These results substantially contribute to the explanation of TL1A's role in inflammation. Our results suggest that TL1A should be considered as a target for immunotherapeutic treatment of rheumatoid arthritis and inflammatory bowel disease.

  19. TCR usage, gene expression and function of two distinct FOXP3(+)Treg subsets within CD4(+)CD25(hi) T cells identified by expression of CD39 and CD45RO.

    Science.gov (United States)

    Ye, Lingying; Goodall, Jane C; Zhang, Libin; Putintseva, Ekaterina V; Lam, Brian; Jiang, Lei; Liu, Wei; Yin, Jian; Lin, Li; Li, Ting; Wu, Xin; Yeo, Giles; Shugay, Mikhail; Chudakov, Dmitriy M; Gaston, Hill; Xu, Huji

    2016-03-01

    FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that expression of CD39 and CD45RO distinguishes three sub-populations within human CD4(+)CD25(hi) T cells. Initial phenotypic and functional analysis demonstrated that CD4(+)CD25(hi)CD39(+)CD45RO(+) cells had properties consistent with effector Treg, CD4(+)CD25(hi)CD39(-)CD45RO(-) cells were naïve Treg and CD4(+)CD25(hi)CD39(-)CD45RO(+) cells were predominantly non-Treg with effector T-cell function. Differences in these two newly identified Treg subsets were corroborated by studies of gene expression and TCR analysis. To apply this approach, we studied these two newly identified Treg subsets in ankylosing spondylitis, and showed impairment in both effector and naïve Treg. This work highlights the importance of discriminating Treg subsets to enable proper comparisons of immune regulatory capacity in healthy individuals and those with inflammatory disease.

  20. THE EXPRESSION OF MEMBRANE INTERLEUKIN-2 RECEPTOR(CD25) ON THE SURFACE OF PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) OF PULMONARY TUBERCULOSIS AND ITS CLINICAL MANIFESTATION%肺结核病患者PBMC膜白介素-2受体(CD25)表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    王健; 蔡茹; 刘智; 刘炳祥

    2003-01-01

    目的:探讨外周血单个核细胞(PBMC)膜白介素-2受体mIL-2R,(CD25)表达在肺结核病鉴别诊断中的应用价值.方法:用生物素-链霉亲和素(BSA)法检测肺结核、支气管肺炎患者T细胞亚群及植物血凝素(PHA)诱导前后CD25表达水平.结果:支气管肺炎患者CD+3、CD+4、CD+8水平分别为(62.32±6.34)%、(47.52±7.16)%、(32.12±6.55)%,CD+4/CD+8比值为1.52±0.43,PHA诱导前后CD25水平分别为(4.56±1.52)%、(35.12±7.21)%.空洞型肺结核CD+3、CD+4、CD+8、CD+4/CD+8水平分别为(41.13±5.25)%、(43.38±5.15)%、(36.25±3.46)%和1.15±0.21,非空洞型肺结核CD+3、CD+4、CD+8、CD+4/CD+8水平分别为(46.29±5.60)%、(47.21±4.86)%、(32.36±4.03)%、1.46±0.25,相互比较CD+3、CD+3/CD+8差异均有显著性(P<0.01和P<0.05).空洞型肺结核与非空洞型肺结核患者PHA诱导前后CD25水平分别为(2.13±1.14)%、(27.25±3.50)%和(3.43±1.35)%、(31.14±4.11)%,两者相比差异均有显著性(P<0.01).结论:肺结核病患者体内存在明显的细胞免疫功能紊乱 ,主要表现为CD25表达水平降低,CD25表达水平与肺结核病的病情似有一定关系,其对肺结核病鉴别诊断具有重要价值.

  1. Expression and significance of aryl hydrocarbon receptor in peripheral blood CD4+CD25+T of rheumatoid arthritis%芳香烃受体在类风湿关节炎患者外周血CD4+CD25+T细胞的表达及意义

    Institute of Scientific and Technical Information of China (English)

    程琳; 钱龙; 谭悦; 李向培; 厉小梅; 汪国生

    2016-01-01

    目的 以类风湿关节炎(rheumatoid arthritis,RA)患者为研究对象,观察芳香烃受体(aryl hydrocarbon receptor,AHR)在患者外周血CD4+CD25+T细胞中的表达水平,探讨AHR在RA发病机制中的意义.方法 采用流式细胞术检测RA患者(35例)及健康对照组(14例)中AHR阳性细胞在外周血CD4+CD25+T及CCR6+CD4+T细胞中所占比例,并将所得结果与患者临床指标的相关性做分析.结果 RA组外周血CD4+ CD25+T细胞中AHR阳性细胞所占比例为(17.90(6.10,80.10))%,低于健康对照组(52.43(19.18,96.43))%,差异有统计学意义(Z=-4.362,P<0.001);正常对照组外周血CD4+ CD25+T细胞中AHR阳性细胞比例为(52.49±19.18)%,高于CCR6+ CD4+T细胞中(23.18±5.62)%,且都高于外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)中(18.06±7.80)%,三组间差异有统计学意义(x2=24.03,P<0.001);RA组CD4+ CD25+T细胞中的AHR比例为(17.90(6.10,80.10))%,低于PBMCs中的(34.43(8.72,56.37))%,且都低于CCR6+CD4+T细胞中的(46.15(20.18,87.31))%,三组间差异有统计学意义(x2=38.29,P<0.001).结论 RA外周血CD4+CD25+T细胞中,AHR阳性细胞比例降低,而在CCR6+ CD4+T细胞中升高,AHR可能通过调节辅助性T细胞17与调节性T细胞细胞的分化,影响Th17与Treg之间的平衡,从而参与RA的发病机制.

  2. The Expression of CD25 and FOXP3 in Mouse Asthma and the Effect of Dexamethasone%CD25及FOXP3在支气管哮喘小鼠中的表达以及地塞米松的干预作用

    Institute of Scientific and Technical Information of China (English)

    马祥; 梁宗安; 毛辉; 刘雅; 王茂筠

    2010-01-01

    目的 分析哮喘小鼠模型肺组织及骨髓中CD25及FOXP3的表达,以及地塞米松的干预作用.方法 BALB/c小鼠随机分为正常对照、哮喘及地塞米松干预组,通过HE染色观察肺组织的病理变化,应用Western blot、RT-PCR方法检测肺组织FOXP3及CD25的表达,RT-PCR方法检测哮喘及地塞米松干预组肺及骨髓FOXP3 mRNA表达.结果 哮喘及地塞米松干预组肺组织FOXP3表达强于正常对照组(P0.05);哮喘及地塞米松干预组肺组织及骨髓细胞均有FOXP3 mRNA表达,且地塞米松组强于哮喘组(P<0.05).结论 哮喘小鼠肺内CD25及FOXP3表达增强,地塞米松会促进其表达;哮喘小鼠骨髓有F10XP3表达,地塞米松促进其表达.

  3. Influence of functional groups on the C{sub {alpha}-}C{sub {beta}}chain of L-phenylalanine and its derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Aravindhan [Centre for Molecular Simulation, Swinburne University of Technology, P.O. Box 218, Hawthorn, Melbourne, Victoria 3122 (Australia); Brunger, Michael [School of Chemistry, Physics and Earth Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Wang Feng, E-mail: fwang@swin.edu.a [Centre for Molecular Simulation, Swinburne University of Technology, P.O. Box 218, Hawthorn, Melbourne, Victoria 3122 (Australia)

    2010-07-21

    L-phenylalanine (L-phe) consists of three different functional groups, i.e., phenyl, carboxyl (-COOH) and amino (-NH{sub 2}), joining through the C{sub {alpha}-}C{sub {beta}}bridge. Substitution of these groups produces 2-phenethylamine (PEA) and 3-phenylpropionic acid (PPA). Electronic structures of L-phe, PEA and PPA together with smaller 'fragments' L-alanine and benzene were determined using density functional theory (DFT), from which core and valence shell ionization spectra were simulated. Comparison of the spectra reveals that core shell ionization energies clearly indicate that the carbon bridge is significantly affected by their functional group substitutions particularly at the C{sub {alpha}}site. In the valence space, quite unexpectedly, the frontier orbitals are concentrated on the benzene group although some energy splitting is observed. The orbitals which significantly affect the C{sub {alpha}-}C{sub {beta}}carbon backbone are from the inner valence shell in the ionization energy region of 20-26 eV of the molecules.

  4. Feasibility of observing the {\\alpha} decay chains from isotopes of SHN with Z = 128, Z = 126, Z = 124 and Z = 122

    CERN Document Server

    Santhosh, K P; Nithya, C

    2016-01-01

    Taking the Coulomb and proximity potential model for deformed nuclei (CPPMDN) as the interacting potential for the post-scission region, the alpha decay properties of 34 isotopes of the superheavy nuclei with Z = 128 within the range 306 $\\leq$ A $\\leq$ 339 have been studied, considering both the parent and daughter nuclei to be deformed. The manuscript also deals with the decay properties of the isotopes of Z = 126 (within 288 $\\leq$ A $\\leq$ 339), Z = 124 (within 284 $\\leq$A $\\leq$ 339) and Z = 122 (within 280 $\\leq$ A $\\leq$ 339). The alpha decay half lives thus evaluated has been compared with the values evaluated using other theoretical models and it was seen that, our theoretical alpha decay half lives matches well with these values. Through the present study, we have underlined and have established the fact that, among the 192 isotopes considered in the present study, only those isotopes $^{321-324,328-335}$128, $^{318-320,323-327}$126, $^{305-308,315-322}$124 and $^{298-307,311-314}$122 can be synthes...

  5. The influence of allogenetic mesenchymal stem cells transplantation to collagen induced arthritis CD 4 + CD25 + regulatory T cell expression in mice%异基因骨髓间充质干细胞移植对小鼠胶原性关节炎CD4+CD25+调节性T细胞表达的影响

    Institute of Scientific and Technical Information of China (English)

    孙旭; 齐月; 牛广华; 高玉洁; 王柏山; 王思微; 严峰

    2014-01-01

    Objective To study the influence of allogenetic mesenchymal stem cells (MSCs) transplantation on the expression of collagen induced arthritis CD4 + CD25 + regulatory T cell in mice .Methods A total of 40 C57BL/6 (H-2b) mice were selected and randomly divided into normal control group ,model group ,MSCs transplant treatment group and methotrexate treatment of positive control group .Ten mice in each group .Except for mice in the normal control group ,the others were treated with Freund's complete adjuvant + Collagen Ⅱ to induce C57BL/6(H-2b) mice that to make mouse model .Bone marrow mononuclear cells were isolated ,then the MSCs were identified and screened by FAcscaliburTM flow cytometry analyzer .MSCs was transplanted by tail vein injection with the number of cells as 2 × 106 .All the mice in four groups were put to death after transplanting 42 days ,and observed the symptoms and the degree of swelling of the joints .Using flow cytometry to detect the contents of CD4 + CD25 + ,and collected data and made statistical analysis .Results There was no significant difference on the swelling degree of joints between the MSCs transplant treatment group and the normal control group (P> 0 .05) .Compared with methotrexate treatment of positive control group ,there was significant difference on CD4 + CD25 + regulatory T cell expression in the MSCs transplant treatment group (P 0 .05) .Conclusion MSCs transplantion could significantly improve the swelling degree of joints ,and significantly increase the expression of CD4 + CD25 + .Therefore ,MSCs could be used as a new source of replacement cells for transplantation therapy of rheumatoid arthritis .%目的:探讨异基因骨髓间充质干细胞(MSCs)移植对小鼠胶原性关节炎 CD4+、CD25+调节性 T 细胞表达的影响。方法选取40只 C57BL/6(H-2b)小鼠,随机分为正常对照组、Ⅱ型胶原性关节炎(CIA)模型组、MSCs 移植治疗组、甲氨蝶呤

  6. 大肠癌患者外周血CD4+ CD25+ CD127-调节性T细胞表达及其临床意义%Expression and clinical significance of CD4+ CD25+ CD127- regulatory T cells in peripheral blood in patients of colon cancer

    Institute of Scientific and Technical Information of China (English)

    任红; 樊静; 张凤春; 康文喜

    2011-01-01

    目的:探讨CD4+ CD25+ CD127-调节性T细胞在大肠癌患者外周血中的表达水平及临床意义.方法:应用流式细胞仪检测200例大肠癌患者外周血CD4+ CD25+CD127-调节性T细胞占CD4+T细胞的百分比,并分析其与大肠癌组织的分化程度、淋巴结转移和临床分期的关系.结果:大肠癌患者外周血CD4+ CD25+ CD127-调节性T细胞占CD4+T细胞的百分率[(4.84±1.35)%]明显高于健康对照组[(0.85±0.25)%],差异有统计学意义,P<0.05.低分化者外周血调节性T细胞[(4.21±0.42)%]明显高于高分化者[(3.92±0.41)%],差异有统计学意义,P<0.05;有淋巴结转移者外周血调节T细胞[(4.57±1.44)%]明显高于无淋巴结转移者[(2.36±0.68)%],差异有统计学意义,P<0.01;Ⅲ和Ⅳ期患者外周血调节性T细胞[(3.53±1.41)%和(4.38±1.32)%]明显高于Ⅰ~Ⅱ期[(1.90±0.86)%],差异有统计学意义,P<0.01.结论:大肠癌患者外周血CD4+CD25+ CD127调节性T细胞占CD4+T细胞的百分率明显升高,可能在大肠癌的免疫耐受和免疫逃逸中发挥重要作用,检测其结果对于判断大肠癌的病程进展及预后有一定参考价值.%OBJECTIVE: To investigate the levels and clini-cal significance of the CD4+ CD25 + CD127- regulatory T cells in the peripheral blood of the patients of colon cancer. METHODS: To analysis the percentage of CD4 + CD25 + CD127- regulatory T cells in the peripheral blood of 200 patients of colon cancer with flow cytometry. And to study the relations between the percent-age of the regulatory T cells and the differentiation of colon canc-er tissues,lymphatic metastasis and clinical stages of colon canc-er. RESULTS: The percentage of CD4+ CD25 + CD127~ regula-tory T cells in the peripheral blood of the patients of colon cancer was (4. 84 ± 1. 35)% and was significantly higher than that (0.85 ± 0.25)% in healthy control group(P<0. 05). The per-centage of regulatory T cells in poorly differentiated tissues

  7. Dynamic changes in percentages of CD4+CD25+regulatory T cells and Th17 cells in process of airway remodeling in mouse model of asthma%哮喘小鼠气道重塑过程中CD4+CD25+调节性T细胞和Th17细胞表达的动态变化

    Institute of Scientific and Technical Information of China (English)

    娄春艳; 李敏; 李丽

    2015-01-01

    Objective To study the dynamic changes in Th17 cells and CD4+CD25+regulatory T cells (Treg) in the spleen and to analyze their relationship with airway remodeling. Methods A total of 48 female speciifc pathogen-free Balb/c mice were randomly divided into control and asthmatic groups. To establish the asthmatic airway remodeling model, the mice were sensitized to ovalbumin (OVA) through intraperitoneal injection of OVA and aluminum hydroxide suspension and challenged by inhalation of aerosol OVA. The matched control group was treated with normal saline instead. In 24 hours after 2-week, 4-week, and 8-week aerosol inhalation, 8 mice were randomly selected from each group and sacriifced. Then histopathological examination of the left lung was performed to measure the degree of airway remodeling. The percentages of Th17 and CD4+CD25+Treg cells in total CD4+cells from the spleen were determined by lfow cytometry. Results In the asthmatic group, the ratios of total bronchial wall area to bronchial basement membrane perimeter (WAt/Pbm) and bronchial smooth muscle area to bronchial basement membrane perimeter (WAm/Pbm) signiifcantly increased as the challenge proceeds (P<0.01). The percentage of Th17 cells derived from the cell suspension of the spleen gradually increased and it was positively correlated with the degree of asthmatic airway remodeling (P<0.01). The percentage of CD4+CD25+Treg cells from the suspension gradually decreased and it was negatively correlated with the degree of asthmatic airway remodeling (P<0.01). Conclusions In mice with asthma, as the challenge proceeds, the airway remodeling becomes more severe, the percentage of Th17 cells increases, and the percentage of CD4+CD25+Treg cells decreases. The immunological imbalance is possibly one of the important factors inducing airway remodeling.%目的:探讨哮喘小鼠Th17细胞和CD4+CD25+调节性T细胞(Treg)在脾组织中表达水平的变化规律及与气道重塑的关系

  8. Deletion of Fibrinogen-like Protein 2 (FGL-2, a Novel CD4+ CD25+ Treg Effector Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in Mice.

    Directory of Open Access Journals (Sweden)

    Junhua Wang

    2015-05-01

    Full Text Available The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2, a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection.Key parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/- and wild type (AE-WT mice at 1 and 4 month(s post-infection were (i parasite load (i. e. wet weight of parasitic metacestode tissue, and (ii parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions were incubated with CD4+ effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2-/- mice exhibited (as compared to AE-WT-animals (a a significantly lower parasite load with reduced proliferation activity, (b an increased T cell proliferative response to ConA, (c reduced Treg numbers and function, and (d a persistent capacity of Th1 polarization and DC maturation.FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation. Prospectively, targeting FGL2 could

  9. Gaseous [M - H]+ ions of alpha,omega-diphenylalkanes: cyclization to [M + H]+ type ions of benzocycloalkanes as recognized by chain-length dependent proton exchange

    OpenAIRE

    Kuck, Dietmar

    1992-01-01

    Metastable [M - H]+ ions of alpha,omega-diphenylalkanes C6H5(CH2)xC6H5 where x = 3-6 (structures 3-6 respectively), generated by hydride abstraction in the chemical ionization (i-butane) source, eliminate benzene after proton exchange between the aromatic rings. The proton exchange is slow for ions [3 - H]+ and [4 - H]+, but fast and apparently complete for ions [5 - H]+ and [6 - H]+. These observations, combined with collision activation experiments, suggest the cyclization of the [M - H]+ i...

  10. Study of Four-Week Aerobic Endurance Exercise on the Induction of CD4+CD25+Treg in Mouse Spleen%4周有氧耐力运动对小鼠脾脏CD4+CD25+调节性T细胞诱导表达的实验研究

    Institute of Scientific and Technical Information of China (English)

    王杰龙; 陈军; 吴明方; 张光波; 陈礼文; 赵建萍

    2012-01-01

    目的:通过对4周负重游泳运动前、后小鼠脾脏CD4- CD25+ Treg表达水平变化及相关细胞因子IL-2、IL-10和TGF-β1水平变化的分析,探讨和研究有氧耐力运动对小鼠脾脏CD4+ CD25+ Treg表达及细胞因子IL-2、IL-10和TGF-β的影响.方法:KM种雄性小鼠100只随机分为对照组(50只)和运动组(50只).运动各组分别按运动方案进行45 min的负重(5%体重)游泳运动每天1次,每周6次.分别于实验前、每周末次运动后24 h,处死小鼠,摘取脾脏和胸腺、采集血样.计算脾指数和胸腺指数,流式细胞仪检测小鼠脾脏CD4+CD25+ Treg的表达,ELISA法测定血清IL-2、IL-10和TGF-β含量.结果:在4周负重游泳运动过程中,运动组小鼠脾指数在第1周末增加并在随后2、3、4周表现出下降的趋势,胸腺指数表现为逐周减少.运动组小鼠脾脏CD4+ CD25+ Treg的表达率表现为逐周增高,运动3周组、4周组高于运动0周组和对照组(P<0.05).运动2周组和3周组血清IL-2水平升高,高于对照组(P<0.05);运动3周组和4周组血清IL-10和TGF-β1水平高于对照组(P<0.05).结论:4周有氧耐力游泳运动可延缓小鼠脾脏生长,加快胸腺萎缩,进而影响免疫器官的发育和功能.4周有氧耐力游泳运动可诱导小鼠T细胞活化,脾脏CD4+ CD25+ Treg表达水平提高,血清IL-10和TGF-β1水平升高,诱导免疫偏移.

  11. Coefficient Alpha

    OpenAIRE

    Panayiotis Panayides

    2013-01-01

    Heavy reliance on Cronbach’s alpha has been standard practice in many validation studies. However, there seem to be two misconceptions about the interpretation of alpha. First, alpha is mistakenly considered as an indication of unidimensionality and second, that the higher the value of alpha the better. The aim of this study is to clarify these misconceptions with the use of real data from the educational setting. Results showed that high alpha values can be obtained in multidimensional scale...

  12. Ex vivo generation of human alloantigen-specific regulatory T cells from CD4(posCD25(high T cells for immunotherapy.

    Directory of Open Access Journals (Sweden)

    Jorieke H Peters

    Full Text Available BACKGROUND: Regulatory T cell (Treg based immunotherapy is a potential treatment for several immune disorders. By now, this approach proved successful in preclinical animal transplantation and auto-immunity models. In these models the success of Treg based immunotherapy crucially depends on the antigen-specificity of the infused Treg population. For the human setting, information is lacking on how to generate Treg with direct antigen-specificity ex vivo to be used for immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that in as little as two stimulation cycles with HLA mismatched allogeneic stimulator cells and T cell growth factors a very high degree of alloantigen-specificity was reached in magnetic bead isolated human CD4(posCD25(high Treg. Efficient increases in cell numbers were obtained. Primary allogeneic stimulation appeared a prerequisite in the generation of alloantigen-specific Treg, while secondary allogeneic or polyclonal stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies enriched alloantigen-specificity and cell yield to a similar extent. CONCLUSIONS/SIGNIFICANCE: The ex vivo expansion protocol that we describe will very likely increase the success of clinical Treg-based immunotherapy, and will help to induce tolerance to selected antigens, while minimizing general immune suppression. This approach is of particular interest for recipients of HLA mismatched transplants.

  13. Orally-Induced Intestinal CD4+ CD25+ FoxP3+ Treg Controlled Undesired Responses towards Oral Antigens and Effectively Dampened Food Allergic Reactions.

    Directory of Open Access Journals (Sweden)

    Paola Lorena Smaldini

    Full Text Available The induction of peripheral tolerance may constitute a disease-modifying treatment for allergic patients. We studied how oral immunotherapy (OIT with milk proteins controlled allergy in sensitized mice (cholera toxin plus milk proteins upon exposure to the allergen. Symptoms were alleviated, skin test was negativized, serum specific IgE and IgG1 were abrogated, a substantial reduction in the secretion of IL-5 and IL-13 by antigen-stimulated spleen cells was observed, while IL-13 gene expression in jejunum was down-regulated, and IL-10 and TGF-β were increased. In addition, we observed an induction of CD4+CD25+FoxP3+ cells and IL-10- and TGF-β-producing regulatory T cells in the lamina propria. Finally, transfer experiments confirmed the central role of these cells in tolerance induction. We demonstrated that the oral administration of milk proteins pre- or post-sensitization controlled the Th2-immune response through the elicitation of mucosal IL-10- and TGF-β-producing Tregs that inhibited hypersensitivity symptoms and the allergic response.

  14. Galectin-9 Ameliorates Con A-Induced Hepatitis by Inducing CD4+CD25low/int Effector T-Cell Apoptosis and Increasing Regulatory T Cell Number

    Science.gov (United States)

    Zhang, Mengying; Zhong, Min; Suo, Qifeng

    2012-01-01

    Background T cell-mediated liver damage is a key event in the pathogenesis of many chronic human liver diseases, such as liver transplant rejection, primary biliary cirrhosis, and sclerosing cholangitis. We and other groups have previously reported that galectin-9, one of the β-galactoside binding animal lectins, might be potentially useful in the treatment of T cell-mediated diseases. To evaluate the direct effect of galectin-9 on hepatitis induced by concanavalin A (Con A) administration in mice and to clarify the mechanisms involved, we administered galectin-9 into mice, and evaluated its therapeutic effect on Con A-induced hepatitis. Methodology/Principal Findings Galectin-9 was administrated i.v. to Balb/c mice 30 min before Con A injection. Compared with no treatment, galectin-9 pretreatment significantly reduced serum ALT and AST levels and improved liver histopathology, suggesting an ameliorated hepatitis. This therapeutic effect was not only attributable to a blunted Th1 immune response, but also to an increased number in regulatory T cells, as reflected in a significantly increased apoptosis of CD4+CD25low/int effector T cells and in reduced proinflammatory cytokine levels. Conclusion/Significance Our findings constitute the first preclinical data indicating that interfering with TIM-3/galectin-9 signaling in vivo could ameliorate Con A-induced hepatitis. This strategy may represent a new therapeutic approach in treating human diseases involving T cell activation. PMID:23118999

  15. Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage.

    Directory of Open Access Journals (Sweden)

    Maciej Kwiatek

    Full Text Available The development of pregnancy is possible due to initiation of immune response in the body of the mother resulting in immune tolerance. Miscarriage may be caused by the impaired maternal immune response to paternal alloantigens located on the surface of trophoblast and fetal cells. The aim of the study was to compare the population of circulating dendritic cells (DCs and CD4+CD25+Foxp3+ regulatory T cells (TREGs in the first trimester of a normal pregnancy and in women with recurrent miscarriage and an attempt to determine the relationship between these cells and the role they may play in human reproductive failures. The study was conducted in a group of 33 first trimester pregnant women with recurrent miscarriage and in a group of 20 healthy pregnant women in the first trimester of normal pregnancy. Among mononuclear cells isolated from peripheral blood, the populations of DCs and TREGs were assessed by flow cytometry. The percentage of myeloid DCs and lymphoid DCs showed no significant difference between study and control group. Older maternal age and obesity significantly reduced the pool of circulating myeloid and lymphoid DCs (R=-0.39, p=0.02. In miscarriages the percentage of circulating TREGs was significantly lower compared to normal pregnancies (p=0.003. Among the analysed factors the percentage of TREGs was the most sensitive and the most specific parameter which correlated with the pregnancy loss. The reduction in the population of circulating TREGs suggests immunoregulatory mechanisms disorder in a pregnancy complicated by miscarriage.

  16. CD4+CD25+CD127 regulatory cells play multiple roles in maintaining HIV-1 p24 production in patients on long-term treatment: HIV-1 p24-producing cells and suppression of anti-HIV immunity

    Directory of Open Access Journals (Sweden)

    Yan-Mei Jiao

    2015-08-01

    Conclusions: CD4+CD25+CD127 regulatory cells play multiple roles in maintaining HIV-1 p24 production in long-term ART patients. Treg cells may be a target for eliminating the latent HIV reservoir after effective long-term ART.

  17. Role of glucagon-like peptide-1 analogue liraglutide played in the proliferation of CD4~+ CD25~- T cells in normal people and type 1 diabetic patients in vitro

    Institute of Scientific and Technical Information of China (English)

    胡瑛

    2013-01-01

    Objective To study the role of glucagon-like peptide-1 (GLP-1) analogue liraglutide played in the proliferation of CD4+CD25-T cells in normal people and newly-onset type 1 diabetic patients,and to evaluate the possible immune regulatory role of liraglutide in the

  18. Research progress of CD+4 CD+25 Foxp3 Treg cells in the hematological malignancies%调节性T细胞在血液系统恶性肿瘤中的研究进展

    Institute of Scientific and Technical Information of China (English)

    邵亮; 张铀

    2008-01-01

    胸腺产生的CD+4 CD25调节性T细胞(Treg细胞)被认为在控制自身免疫、防止移植物排斥反应、抑制抗感染自身免疫以及抑制异基因免疫反应中发挥重要作用.最近有报道此类细胞有抑制机体抗肿瘤的作用.Foxp3是Treg细胞最具特异性的蛋白分子标志物.阐述了血液系统恶性肿瘤患者CD+4 CD+25 Foxp3 Treg的表达以及其对免疫治疗的潜在作用.%Thymus derived CD+4; CD+25 regulatory T cells (Treg) are thought to be specific T cells that play an important role in controlling autoimmunity, preventing transplant rejection, restraining anti-infectious immune response, suppressing allogeneic immune respons. More recently, these cells are reported to have the ability of suppressing antitumor immune response. Foxp3 are the most specific protein of Treg. In this review, we will discuss the expression of CD+4 CD+25 Treg in patients with hematological malignancies and its implication for immunotherapy.

  19. CD4 + CD25 + regulatory T cells-induced tolerance of islet transplantation by targeting OX40/ OX40L costimulation pathway%靶向OX40/OX40L通路对CD4+CD25+调节性T细胞诱导移植耐受的影响

    Institute of Scientific and Technical Information of China (English)

    陈恕求; 许斌; 任全; 王奕铎; 王旭辉; 李宪昌; 陈明

    2012-01-01

    目的 观察OX40/OX40L共刺激通路在调节性T细胞(Treg)诱导移植耐受中的作用.方法 建立小鼠胰岛移植模型,分3组:IgG组、抗-OX40L单抗(RM134L)+抗-CD154单抗( MR1)组、联合RM134L+ MR1及抗-CD25单抗(PC61)组.存活超过150 d小鼠切除移植侧肾脏,在对侧行同或不同主要组织相容性复合体( MHC)的2次胰岛移植.观察各组平均存活时间(MST).检测效应性T细胞(Teff)、野生型和CD154敲除小鼠Treg OX40表达.检测同基因小鼠胰岛、胰岛移植不加或加RM134L+ MR1治疗的移植物内Foxp3表达.Treg与Teff加或不加OX40激动剂(OX86)以不同比例共培养,检测Teff增殖抑制情况.结果 RM134L+ MR1组MST为>150 d(n =8),较IgG组(19d,n=5)和联合PC61组(23 d,n=4)明显延长(P<0.05).同或不同MHC的2次胰岛移植MST分别为>60 d(n=3)和17 d(n =3) (P <0.05).OX40在Teff不表达,在野生型和CD154敲除小鼠Treg表达.3组小鼠胰岛移植物内Foxp3相对表达量分别为8、21、123 AU(P <0.05).Teff与Treg以1∶2和1∶4共培养,β-液体闪烁计数仪测定Teff的核素每分钟计数(CPM)分别为63×103和41×103,与对照组(140×103)比较增殖受抑制(P<0.05),加OX86时CPM值分别为128×103和135×103 (P >0.05).结论 CD4+ CD25+ Treg在诱导移植耐受中发挥重要作用,OX40在其中发挥负性调节作用.%Objective To observe the role of OX40/OX40L costimulation pathway in the CD4+CD25 + regulatory T (Treg) cells-induced tolerance of islet transplantation.Methods Diabetes mellitus was induced in C57BL/6 mice as recipients,and islets from DBA/2 mice were transplanted into the C57BL/6 mice.The recipients were divided into three groups (n =8):treated with IgG as controls,antiOX40L mAb (RM134L) + anti-CD154 mAb (MR1),and RM134L + MR1 + anti-CD25 mAb.The mean survival time (MST) of allograft was observed.The expression of OX40 in T effector cells,Treg cells of wide type and CD154 knock-out mice was detected.The expression of Foxp3 gene in

  20. Th17细胞与Treg细胞在支气管哮喘发病机制中的研究进展%Th17 cell and CD4 + CD25 + Treg in iathogenesis of asthma

    Institute of Scientific and Technical Information of China (English)

    姚斌

    2012-01-01

    近年来,众多研究发现支气管哮喘的发病机制已不能单纯用Th1/Th2平衡理论来解释,CD4+ CD25+调节性T细胞和Th17细胞及其细胞因子IL-10、IL-17、转化生长因子-β等与支气管哮喘发病明显相关.由于Th17细胞与CD4+ CD25+调节性T细胞在功能上相互拮抗,而在分化上密切相关,因此这两种细胞的免疫失衡也是支气管哮喘发病的重要原因.糖皮质激素可通过维甲酸相关孤核受体γt信号途径降低IL-17的表达,还可以通过诱导转录因子Foxp3的表达调控CD4+ CD25+调节性T细胞的分化和功能.%Many studies have suggested that pathogenesis of asthma could no longer be interpreted merely by “Th1/Th2 balance” theory.CD4 + CD25 + Treg and Th17 cells,as well as their cytokines such as IL-10,transforming growth factor-β,and IL-17,account for asthma.CD4 + CD25 + Treg and Th17 are functionally antagonistic to each other,and also go with each other during their differentiation.Therefore,immunity-unbalance of CD4 + CD25 + Treg and Th17 is one of the most important factors that triggers asthma.Glucocorticoid has been shown to down regulate IL-17 expression by retinoic acid receptors γt signaling pathway,and regulate differentiation and function of CD4 + CD25 + Treg by inducing expression of transcription factor Foxp3,all of these are immuno-mechanisms of glucocorticoid in asthma treatment.

  1. Plasmodium falciparum-mediated induction of human CD25Foxp3 CD4 T cells is independent of direct TCR stimulation and requires IL-2, IL-10 and TGFbeta.

    Directory of Open Access Journals (Sweden)

    Anja Scholzen

    2009-08-01

    Full Text Available CD4(+CD25(+Foxp3(+ regulatory T cells (Tregs regulate disease-associated immunity and excessive inflammatory responses, and numbers of CD4(+CD25(+Foxp3(+ Tregs are increased during malaria infection. The mechanisms governing their generation, however, remain to be elucidated. In this study we investigated the role of commonly accepted factors for Foxp3 induction, TCR stimulation and cytokines such as IL-2, TGFbeta and IL-10, in the generation of human CD4(+CD25(+Foxp3(+ T cells by the malaria parasite Plasmodium falciparum. Using a co-culture system of malaria-infected red blood cells (iRBCs and peripheral blood mononuclear cells from healthy individuals, we found that two populations of Foxp3(hi and Foxp3(int CD4(+CD25(hi T cells with a typical Treg phenotype (CTLA-4(+, CD127(low, CD39(+, ICOS(+, TNFRII(+ were induced. Pro-inflammatory cytokine production was confined to the Foxp3(int subset (IFNgamma, IL-4 and IL-17 and inversely correlated with high relative levels of Foxp3(hi cells, consistent with Foxp3(hi CD4 T cell-mediated inhibition of parasite-induced effector cytokine T cell responses. Both Foxp3(hi and Foxp3(int cells were derived primarily from proliferating CD4(+CD25(- T cells with a further significant contribution from CD25(+Foxp3(+ natural Treg cells to the generation of the Foxp3(hi subset. Generation of Foxp3(hi, but not Foxp3(int, cells specifically required TGFbeta1 and IL-10. Add-back experiments showed that monocytes expressing increased levels of co-stimulatory molecules were sufficient for iRBC-mediated induction of Foxp3 in CD4 T cells. Foxp3 induction was driven by IL-2 from CD4 T cells stimulated in an MHC class II-dependent manner. However, transwell separation experiments showed that direct contact of monocytes with the cells that acquire Foxp3 expression was not required. This novel TCR-independent and therefore antigen-non specific mechanism for by-stander CD4(+CD25(hiFoxp3(+ cell induction is likely to reflect a

  2. CD4+CD25+调节性T细胞及其相关蛋白Foxp3在小儿支原体肺炎患者中的表达

    Institute of Scientific and Technical Information of China (English)

    袁浩; 周毅峰; 曹友德; 陈雪初; 马玲飞

    2013-01-01

    目的 探讨不同滴度时小儿肺炎支原体(MP)感染患儿外周血CD4+CD25+Treg细胞和CD4+Foxp3+Treg细胞变化及其临床意义.方法 采用流式细胞分析法分别检测MP感染患儿76例,其中MP抗体IgM阳性滴度1:80 26例,1:160 17例,1:320 15例,1:640 18例和24例健康体检者(对照组)外周血CD4+CD25+Treg细胞,CD4+Foxp3+Treg细胞的表达水平.结果 MP感染患儿1:80组CD4+CD25+Treg、CD4+Foxp3+Treg细胞均明显高于1:640组和对照组(P0.05),CD4+CD25+Treg细胞及CD4+Foxp3+Treg细胞的变化与滴度的变化均呈负相关(r=-0.402、-0.376,P<0.01),CD4+Foxp3+Treg细胞的变化与CD4+CD25+Treg细胞的变化呈正相关(r=0.627,P<0.01).结论 CD4+CD25+ Treg细胞和CD4+Foxp3+Treg细胞在小儿MP感染低滴度组发病初期显著升高,但在高滴度组升高并不明显,且两种细胞的变化与滴度的变化呈负相关,Foxp3蛋白可能是CD4+CD25+Treg特异性的标志.

  3. Alpha-decay branching ratios to high-lying excited-states of the 242Cm→238pu→ 234U →230Th→226Rn decay chain

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jin-Juan; XU Chang; REN Zhong-Zhou

    2009-01-01

    We present a systematic calculation on the 0c-decay branching ratios to excited-states of an even-even α-decay chain 242Cm→238pu→234U →230Th→226Rn by the improved barrier penetration approach. The changes of the parities between the parent nuclei and the daughter nuclei are properly taken into account. The theoretical values are compared with the available experimental data and the deviation between them is within a factor of 5 in most cases.

  4. Pretreatment With Inactivated Bacillus Calmette-Guerin Increases CD4+CD25+ Regulatory T Cell Function and Decreases Functional and Structural Effects of Asthma Induction in a Rat Asthma Model.

    Science.gov (United States)

    Gong, Ping; Li, Yun; Tan, Yu-Pin; Li, Hong

    2016-04-01

    Bacillus Calmette-Guerin (BCG) has been shown to have therapeutic effects on asthma through CD4+CD25+ regulatory T cells (Tregs). We sought to assess pretreatment with inactivated BCG on CD4+CD25+ Tregs and its functional and structural effects in rat asthma model. The rat asthma model was established using ovalbumin (OVA) sensitization and challenge. Ten rats were pretreated with BCG prior to OVA and received continued BCG injections during OVA challenge (BCG+OVA group), 10 rats were treated with OVA alone (OVA group), and 10 rats were treated with saline (control group). After 9 weeks, histamine dihydrochloride effect on airway resistance was measured. Number of CD4+CD25+ Tregs was measured by flow cytometry, expression of Foxp3 and CTLA-4 mRNA was measured, and serum TGF-β levels were determined. Differential cell count in bronchoalveolar lavage fluid (BALF) was determined, and lung tissue was processed and stained with hematoxylin and eosin, Masson's trichrome, and alcine blue and periodic acid Schiff's reaction to evaluate inflammatory cell infiltration, collagen deposition, and presence of goblet cells, respectively. BCG treatment led to an increase in CD4+CD25+ Tregs, as well as an increase in Foxp3 and CTLA-4 expression and serum TGF-β levels. In addition, we observed a decrease in histamine dihydrochloride-induced airway resistance, a decrease in inflammatory leukocytes in BALF, and a decrease in airway remodeling indicators in BCG+OVA-treated rats compared with OVA-treated rats. Intradermally injected inactivated BCG has the potential to improve airway inflammation, airway resistance, and airway remodeling through a mechanism that may involve CD4+CD25+ Tregs. PMID:26495900

  5. 激素抵抗性哮喘患者外周血CD4+CD25+Foxp3+调节性T细胞及IL-10、TGF-β1的变化及意义%Changes and clinical significance of CD4+ CD25+Foxp3+ regulatory T cell and IL-10,TGF-β1 in steroid-resistant asthma patients of peripheral blood

    Institute of Scientific and Technical Information of China (English)

    钱一龙; 赵振中; 朱建俊; 谢中华; 王珠美

    2013-01-01

    目的 观察激素抵抗性哮喘(SRA)患者外周血CD4+ CD25+ Foxp3+调节性T细胞(Treg)及白介素10(IL-10)、转化生长因子β1(TGF-β1)的变化,分析其在SRA发病机制中的作用.方法 采用流式细胞术检测40例SRA患者(激素抵抗组)外周血单个核细胞CD4+ CD25+ Foxp3+ Treg数目,并计算CD4+ CD25+ Foxp3+ Treg占CD4+T淋巴细胞的百分比;酶联免疫吸附试验(ELISA)法检测其血清IL-10、TGF-β1水平,并与激素敏感性患者(激素敏感组,46例)及正常体检者(正常组,30例)进行对比.结果 激素抵抗组患者外周血CD4+ CD25+ Foxp3+ Treg占CD4+T淋巴细胞的百分比、CD4+ CD25+Foxp3+ Treg绝对值及血清IL-10、TGF-β1水平均明显低于激素敏感组与正常组(P<0.01,P<0.05);激素敏感组患者外周血CD4+ CD25+ Foxp3+ Treg占CD4+T淋巴细胞的百分比、CD4+ CD25+ Foxp3+Treg绝对值及血清TGF-β1水平明显低于正常组(P<0.01,P<0.05),血清IL-10无明显差异(P>0.05);CD4+ CD25+ Foxp3+ Treg/CD4+T及CD4+ CD25+ Foxp3+ Treg绝对数均与血清IL-10、TGF-β1水平呈明显正相关(P<0.01).结论 SRA患者外周血CD4+ CD25+ Foxp3+ Treg数目减少及IL-10、TGF-β1含量减低可能与SRA的发生、发展有关.%Objective To investigate the changes of CD4+ CD25+ Foxp3+ regulatory T cell and IL-10,TGF-β1 in steroid-resistant asthma patients of peripheral blood,to study their significance.Methods The CD4+ CD25+ Foxp3+ regulatory T cell in 40 cases steroid-resistant asthma patients were detected by flow cytometry.The levels of serum IL-10 and TGF-β1 were detected by ELISA.The control groups were 30 individuals having general physical examination and 46 patients with steroid-sensitive patients.Results The proportion and number of CD4+ CD25+ Foxp3+ regulatory T cell and the levels of serum IL-10,TGF-β1 in steroid-resistant asthma group of Peripheral Blood were decreased significantly than steroid-sensitive group and healthy control group (P <0.01,P <0

  6. Change of CD4+ CD25+ regulatory T cell and expression of Foxp3 in a mouse model of asthma%哮喘小鼠CD4+CD25+调节性T细胞及Foxp3表达的变化

    Institute of Scientific and Technical Information of China (English)

    李茜; 沈华浩

    2008-01-01

    目的 探讨哮喘小鼠CD4+CD25+调节性T细胞数量的变化及相关转录因子Foxp3表达的变化.方法 24只5周龄C57BL/6小鼠随机分为哮喘模型组和对照组,每组12只,于第0天和第14天,哮喘组以腹腔注射致敏液[0.1%的鸡卵蛋白(OVA)0.1ml与等体积液态铝混合]0.2ml致敏,对照组注射等体积生理盐水,第24、25、26天开始雾化吸入1%的OVA(哮喘组)或生理盐水(对照组)进行激发,连续3 d,于最后1次激发后48 h处死小鼠.取脾脏,制备脾细胞悬液,流式细胞术检测脾脏CD4+CD25+T细胞占CD4+T细胞比例.取脾脏组织以RT-PCR和Western blot分别检测脾脏Foxp3 mRNA和蛋白的表达.数据结果以Levene法行方差齐性检验后,进行独立样本的t检验,以P<0.05为差异具有统计学意义.结果 脾脏CD4+CD25+T细胞占CD4+T细胞比例哮喘组为(7.03±2.19)%,对照组为(9.70±2.80)%,哮喘组低于对照组,两者相比差异有统计学意义(P=0.016);脾脏Foxp3 mRNA的表达水平哮喘组为(0.37±0.11),对照组为(0.237±0.118),哮喘组高于对照组,两者相比差异有统计学意义(P=0.009);脾脏Foxp3蛋白的表达水平哮喘组(0.692±0.171),对照组(0.515±0.135),哮喘组高于对照组,两者相比差异有统计学意义(P=0.01).结论 哮喘时抗原对CD4+CD25+T细胞的激活不足,可能在哮喘发病机制中起一定作用.

  7. Integrability and soliton solutions for an inhomogeneous generalized fourth-order nonlinear Schrödinger equation describing the inhomogeneous alpha helical proteins and Heisenberg ferromagnetic spin chains

    International Nuclear Information System (INIS)

    For describing the dynamics of alpha helical proteins with internal molecular excitations, nonlinear couplings between lattice vibrations and molecular excitations, and spin excitations in one-dimensional isotropic biquadratic Heisenberg ferromagnetic spin with the octupole–dipole interactions, we consider an inhomogeneous generalized fourth-order nonlinear Schrödinger equation. Based on the Ablowitz–Kaup–Newell–Segur system, infinitely many conservation laws for the equation are derived. Through the auxiliary function, bilinear forms and N-soliton solutions for the equation are obtained. Interactions of solitons are discussed by means of the asymptotic analysis. Effects of linear inhomogeneity on the interactions of solitons are also investigated graphically and analytically. Since the inhomogeneous coefficient of the equation h=α x+β, the soliton takes on the parabolic profile during the evolution. Soliton velocity is related to the parameter α, distance scale coefficient and biquadratic exchange coefficient, but has no relation with the parameter β. Soliton amplitude and width are only related to α. Soliton position is related to β

  8. 骨髓间充质干细胞对肾病综合征大鼠CD4+CD25+调节性T细胞的影响%Effects of bone marrow mesenchymal stem cell transplantation on CD4+CD25+regulatory T cells in rats with primary nephrotic syndrome

    Institute of Scientific and Technical Information of China (English)

    杨焕丹; 张锐锋; 封东进; 朱冰冰; 吕娟

    2014-01-01

    BACKGROUND:Decreased function and reduced number of CD4+CD25+regulatory T cells have been considered the major manifestation of immunity dysfunction in children with primary nephrotic syndrome. Bone marrow mesenchymal stem cells have immunoregulation effects, which up-regulate CD4+CD25+regulatory T cells, inhibit proliferation of lymphocytes, and have been widely used in many immune diseases. OBJECTIVE:To investigate the effects of bone marrow mesenchymal stem celltransplantation on the CD4+CD25+regulatory T cells of peripheral blood in rats with primary nephrotic syndrome. METHODS:Bone marrow mesenchymal stem cells from six Sprague-Dawley rats were isolated, passaged and utilized for cellsuspension preparation. At the third passage, bone marrow mesenchymal stem cells were used for transplantation. The remaining 30 rats were randomly and equal y divided into three groups:normal group, normal saline infusion group, and bone marrow mesenchymal stem cells group. The rat models of primary nephrotic syndrome were established by single injection of adriamycin intravenously through tail vein in the latter two groups. Rats were then treated with bone marrow mesenchymal stem cells (1×10 7 ) (bone marrow mesenchymal stem cells group) or normal saline (normal saline infusion group) through tail vein at the same time after adriamycin administration. The normal group received no treatment. RESULTS AND CONCLUSION:Compared with the normal group, rats in the normal saline infusion group developed nephropathy characterized by ascites, proteinuria, hypoalbuminemia, hypercholastero-lnemia, and progressive renal injury. However, the proteinurine and clinical severity in bone marrow mesenchymal stem cells group were significantly ameliorated after treatment with bone marrow mesenchymal stem cells. CD4+CD25+Treg/CD4+Treg in the peripheral blood in the bone marrow mesenchymal stem cells group and normal saline infusion group were significantly higher than that in the normal group at 28

  9. 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.

  10. Mesenchymal stem cells alleviate atherosclerosis by elevating number and function of CD4(+)CD25 (+)FOXP3 (+) regulatory T-cells and inhibiting macrophage foam cell formation.

    Science.gov (United States)

    Wang, Zhi Xiao; Wang, Chong Quan; Li, Xiao Yan; Feng, Gao Ke; Zhu, Hong Ling; Ding, Yan; Jiang, Xue Jun

    2015-02-01

    Atherosclerosis is a chronic inflammatory disease characterized by the formation of plaques inside arteries, leading to narrowing and blockage. Potential therapeutic strategies include expanding the population of regulatory T-cells (Tregs) to enhance atheroprotective immunity, and inhibiting the formation of macrophage foam cells. Here, we studied the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on atherosclerotic plaque formation in Apolipoprotein E(-/-) (ApoE-KO) mice, and elucidated the underlying mechanism. BM-MSCs isolated from 4 week-old ApoE-KO mice were evaluated by flow cytometry for expression of MSC-specific markers. Thirty eight week-old ApoE-KO mice were randomly divided into three experimental groups (n = 10 per group): 1. MSC group-received BM-MSCs intravenously; 2. Vehicle group-received DMEM; 3. Control group-did not receive any treatment. Administration of MSCs resulted in a marked decrease in the size of atherosclerotic plaques 3 months after treatment. In addition, the number and function of CD4(+)CD25(+)FOXP3(+) regulatory T-cells (Tregs) in cultured splenocytes, and the expression of FOXP3 at both mRNA and protein levels, was significantly increased in the MSC group. In vitro experiments further indicated that the formation of macrophage foam cells was inhibited by treatment with MSCs, accompanied by a significant downregulation in CD36 and scavenger receptor A (SRA). Our findings suggest that MSCs play an atheroprotective role by enhancing the number and function of Tregs and inhibiting the formation of macrophage foam cells. Hence, administration of MSCs to atherosclerotic patients might have significant clinical benefits.

  11. Effects of active bufadienolide compounds on human cancer cells and CD4+CD25+Foxp3+ regulatory T cells in mitogen-activated human peripheral blood mononuclear cells.

    Science.gov (United States)

    Yuan, Bo; He, Jing; Kisoh, Keishi; Hayashi, Hideki; Tanaka, Sachiko; Si, Nan; Zhao, Hai-Yu; Hirano, Toshihiko; Bian, Baolin; Takagi, Norio

    2016-09-01

    The growth inhibitory effects of bufadienolide compounds were investigated in two intractable cancer cells, a human glioblastoma cell line U-87 and a pancreatic cancer cell line SW1990. Among four bufadienolide compounds, a dose-dependent cytotoxicity was observed in these cancer cells after treatment with gamabufotalin and arenobufagin. The IC50 values of the two compounds were 3-5 times higher in normal peripheral blood mononuclear cells (PBMCs) than these values for both cancer cell lines. However, similar phenomena were not observed for two other bufadienolide compounds, telocinobufagin and bufalin. These results thus suggest that gamabufotalin and arenobufagin possess selective cytotoxic activity against tumor cells rather than normal cells. Moreover, a clear dose-dependent lactate dehydrogenase (LDH) release, a well-known hallmark of necrosis, was observed in both cancer cells treated with gamabufotalin, suggesting that gamabufotalin-mediated cell death is predominantly associated with a necrosis-like phenotype. Of most importance, treatment with as little as 8 ng/ml of gamabufotalin, even an almost non-toxic concentration to PBMCs, efficiently downregulated the percentages of CD4+CD25+Foxp3+ regulator T (Treg) cells in mitogen-activated PBMCs. Given that Treg cells play a critical role in tumor immunotolerance by suppressing antitumor immunity, these results suggest that gamabufotalin may serve as a promising candidate, as an adjuvant therapeutic agent by manipulating Treg cells to enhance the efficacy of conventional anticancer drugs and lessen their side-effects. These findings provide insights into the clinical application of gamabufotalin for cancer patients with glioblastoma/pancreatic cancer based on its cytocidal effect against tumor cells as well as its depletion of Treg cells. PMID:27431260

  12. CD4+CD25+Foxp3+ regulatory T cells depletion may attenuate the development of silica-induced lung fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Fangwei Liu

    Full Text Available BACKGROUND: Silicosis is an occupational lung disease caused by inhalation of silica dust characterized by lung inflammation and fibrosis. Previous study showed that Th1 and Th2 cytokines are involved in silicosis, but Th1/Th2 polarization during the development of silicosis is still a matter of debate. Regulatory T cells (Treg cells represent a crucial role in modulation of immune homeostasis by regulating Th1/Th2 polarization, but their possible implication in silicosis remains to be explored. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the implication of Treg cells in the development of silicosis, we generated the Treg-depleted mice model by administration of anti-CD25 mAbs and mice were exposed to silica by intratracheal instillation to establish experimental model of silica-induced lung fibrosis. The pathologic examinations show that the Treg-depleted mice are susceptive to severer inflammation in the early stage, with enhanced infiltration of inflammatory cells. Also, depletion of Treg cells causes a delay of the progress of silica-induced lung fibrosis in mice model. Further study of mRNA expression of cytokines reveals that depletion of Tregs leads to the increased production of Th1-cytokines and decreased production of Th2-cytokine. The Flow Cytometry and realtime PCR study show that Treg cells exert the modulation function both directly by expressing CTLA-4 at the inflammatory stage, and indirectly by secreting increasing amount of IL-10 and TGF-β during the fibrotic stage in silica-induced lung fibrosis. CONCLUSION/SIGNIFICANCE: Our study suggests that depletion of Tregs may attenuate the progress of silica-induced lung fibrosis and enhance Th1 response and decelerate Th1/Th2 balance toward a Th2 phenotype in silica-induced lung fibrosis. The regulatory function of Treg cells may depend on direct mechanism and indirect mechanism during the inflammatory stage of silicosis.

  13. Adalimumab ameliorates OVA-induced airway inflammation in mice: Role of CD4(+) CD25(+) FOXP3(+) regulatory T-cells.

    Science.gov (United States)

    Elsakkar, Mohamed G; Sharaki, Olla A; Abdallah, Dina M; Mostafa, Dalia K; Shekondali, Fadia T

    2016-09-01

    Asthma is a chronic inflammatory heterogeneous disorder initiated by a dysregulated immune response which drives disease development in susceptible individuals. Though T helper 2 (TH2) biased responses are usually linked to eosinophilic asthma, other Th cell subsets induce neutrophilic airway inflammation which provokes the most severe asthmatic phenotypes. A growing evidence highlights the role of T regulatory (Treg) cells in damping abnormal Th responses and thus inhibiting allergy and asthma. Therefore, strategies to induce or augment Treg cells hold promise for treatment and prevention of allergic airway inflammation. Recently, the link between Tumor necrosis factor-α (TNF-α) and Treg has been uncovered, and TNF-α antagonists are increasingly used in many autoimmune diseases. Yet, their benefits in allergic airway inflammation is not clarified. We investigated the effect of Adalimumab, a TNF-α antagonist, on Ovalbumin (OVA)-induced allergic airway inflammation in CD1 mice and explored its impact on Treg cells. Our results showed that Adalimumab treatment attenuated the OVA-induced increase in serum IgE, TH2 and TH1 derived inflammatory cytokines (IL-4 and IFN-γ, respectively) in bronchoalveolar lavage (BAL) fluid, suppressed recruitment of inflammatory cells in BAL fluid and lung, and inhibited BAL fluid neutrophilia. It also ameliorated goblet cell metaplasia and bronchial fibrosis. Splenocytes flow cytometry revealed increased percentage of CD4(+) CD25(+) FOXP3(+) Treg cells by Adalimumab that was associated with increase in their suppressive activity as shown by elevated BAL fluid IL-10. We conclude that the beneficial effects of Adalimumab in this CD1 neutrophilic model of allergic airway inflammation are attributed to augmentation of Treg cell number and activity. PMID:27262379

  14. Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chain

    Directory of Open Access Journals (Sweden)

    Braun Sandra

    2002-08-01

    Full Text Available Abstract Background Although IL-4 and IL-13 share the IL-13 receptor, IL-13 exhibits unique functions. To elicit the cellular basis of these differences, signal transduction processes have been compared. Additionally, the role of the IL-4 receptor alpha (IL-4Rα variant Q551R was investigated. Methods Peripheral blood mononuclear cells from donors were stimulated with IL-4 and IL-13. The phosphorylation status of effector substrates was detected by immunostaining. Binding of SHP-2 to IL-4Rα was investigated by using synthetic peptides. Results SHP-2 bound IL-4Rα synthetic peptide; this binding was reduced in the presence of the R551 variant. Stimulation with IL-4 increased SHP-1 phosphorylation, however, stimulation with IL-13 increased SHP-2 phosphorylation. PI3-kinase phosphorylation was elevated following stimulation with IL-13 in all individuals and with IL-4 only in R551 individuals. Jak1, Tyk2 and IRS-2 signals were reduced after IL-13 stimulation in Q551 individuals. STAT3 phosphorylation was markedly increased in R551 individuals, following stimulation with both IL-4 and IL-13. However, STAT3 was only detected immediately in nuclear extracts from variant individuals after stimulation with IL-13; in wildtype individuals STAT3 was only detected after IL-4 treatment. Conclusion IL-4 and IL-13 appear to promote distinct signal transduction cascades. SHP-1 seems to be predominately activated by IL-4 and to influence the PI3-kinase, in contrast, SHP-2 seems to be predominately activated by IL-13 and to influence Jak1, Tyk2 and IRS-2. Both phosphatases control STAT3. In the presence of the variant R551, SHP-1/2 activation is reduced and signal transduction is altered. STAT3 signaling appears be further regulated on the level of nuclear translocation.

  15. Isolation of highly suppressive CD25+FoxP3+ T regulatory cells from G-CSF-mobilized donors with retention of cytotoxic anti-viral CTLs: application for multi-functional immunotherapy post stem cell transplantation.

    Science.gov (United States)

    Samuel, Edward R; Beloki, Lorea; Newton, Katy; Mackinnon, Stephen; Lowdell, Mark W

    2014-01-01

    Previous studies have demonstrated the effective control of cytomegalovirus (CMV) infections post haematopoietic stem cell transplant through the adoptive transfer of donor derived CMV-specific T cells (CMV-T). Strategies for manufacturing CMV immunotherapies has involved a second leukapheresis or blood draw from the donor, which in the unrelated donor setting is not always possible. We have investigated the feasibility of using an aliquot of the original G-CSF-mobilized graft as a starting material for manufacture of CMV-T and examined the activation marker CD25 as a targeted approach for identification and isolation following CMVpp65 peptide stimulation. CD25+ cells isolated from G-CSF-mobilized apheresis revealed a significant increase in the proportion of FoxP3 expression when compared with conventional non-mobilized CD25+ cells and showed a superior suppressive capacity in a T cell proliferation assay, demonstrating the emergence of a population of Tregs not present in non-mobilized apheresis collections. The expansion of CD25+ CMV-T in short-term culture resulted in a mixed population of CD4+ and CD8+ T cells with CMV-specificity that secreted cytotoxic effector molecules and lysed CMVpp65 peptide-loaded phytohaemagglutinin-stimulated blasts. Furthermore CD25 expanded cells retained their suppressive capacity but did not maintain FoxP3 expression or secrete IL-10. In summary our data indicates that CD25 enrichment post CMV stimulation in G-CSF-mobilized PBMCs results in the simultaneous generation of both a functional population of anti-viral T cells and Tregs thus illustrating a potential single therapeutic strategy for the treatment of both GvHD and CMV reactivation following allogeneic haematopoietic stem cell transplantation. The use of G-CSF-mobilized cells as a starting material for cell therapy manufacture represents a feasible approach to alleviating the many problems incurred with successive donations and procurement of cells from unrelated donors

  16. Requirement of cognate CD4+ T-cell recognition for the regulation of allospecific CTL by human CD4+ CD127- CD25+ FOXP3+ cells generated in MLR.

    Directory of Open Access Journals (Sweden)

    Yuming Yu

    Full Text Available Although immunoregulation of alloreactive human CTLs has been described, the direct influence of CD4(+ Tregs on CD8(+ cytotoxicity and the interactive mechanisms have not been well clarified. Therefore, human CD4(+CD127(-CD25(+FOXP3(+ Tregs were generated in MLR, immunoselected and their allospecific regulatory functions and associated mechanisms were then tested using modified (51Chromium release assays (Micro-CML, MLRs and CFSE-based multi-fluorochrome flow cytometry proliferation assays. It was observed that increased numbers of CD4(+CD127(-CD25(+FOXP3(+ cells were generated after a 7 day MLR. After immunoselection for CD4(+CD127(-CD25(+ cells, they were designated as MLR-Tregs. When added as third component modulators, MLR-Tregs inhibited the alloreactive proliferation of autologous PBMC in a concentration dependent manner. The inhibition was quasi-antigen specific, in that the inhibition was non-specific at higher MLR-Treg modulator doses, but non-specificity disappeared with lower numbers at which specific inhibition was still significant. When tested in micro-CML assays CTL inhibition occurred with PBMC and purified CD8(+ responders. However, antigen specificity of CTL inhibition was observed only with unpurified PBMC responders and not with purified CD8(+ responders or even with CD8(+ responders plus Non-T "APC". However, allospecificity of CTL regulation was restored when autologous purified CD4(+ T cells were added to the CD8(+ responders. Proliferation of CD8(+ cells was suppressed by MLR-Tregs in the presence or absence of IL-2. Inhibition by MLR-Tregs was mediated through down-regulation of intracellular perforin, granzyme B and membrane-bound CD25 molecules on the responding CD8(+ cells. Therefore, it was concluded that human CD4(+CD127(-CD25(+FOXP3(+ MLR-Tregs down-regulate alloreactive cytotoxic responses. Regulatory allospecificity, however, requires the presence of cognate responding CD4(+ T cells. CD8(+ CTL regulatory

  17. Recoil-alpha-fission and recoil-alpha-alpha-fission events observed in the reaction Ca-48 + Am-243

    CERN Document Server

    Forsberg, U; Andersson, L -L; Di Nitto, A; Düllmann, Ch E; Gates, J M; Golubev, P; Gregorich, K E; Gross, C J; Herzberg, R -D; Hessberger, F P; Khuyagbaatar, J; Kratz, J V; Rykaczewski, K; Sarmiento, L G; Schädel, M; Yakushev, A; Åberg, S; Ackermann, D; Block, M; Brand, H; Carlsson, B G; Cox, D; Derkx, X; Dobaczewski, J; Eberhardt, K; Even, J; Fahlander, C; Gerl, J; Jäger, E; Kindler, B; Krier, J; Kojouharov, I; Kurz, N; Lommel, B; Mistry, A; Mokry, C; Nazarewicz, W; Nitsche, H; Omtvedt, J P; Papadakis, P; Ragnarsson, I; Runke, J; Schaffner, H; Schausten, B; Shi, Y; Thörle-Pospiech, P; Torres, T; Traut, T; Trautmann, N; Türler, A; Ward, A; Ward, D E; Wiehl, N

    2015-01-01

    Products of the fusion-evaporation reaction Ca-48 + Am-243 were studied with the TASISpec set-up at the gas-filled separator TASCA at the GSI Helmholtzzentrum f\\"ur Schwerionenforschung. Amongst the detected thirty correlated alpha-decay chains associated with the production of element Z=115, two recoil-alpha-fission and five recoil-alpha-alpha-fission events were observed. The latter are similar to four such events reported from experiments performed at the Dubna gas-filled separator. Contrary to their interpretation, we propose an alternative view, namely to assign eight of these eleven decay chains of recoil-alpha(-alpha)-fission type to start from the 3n-evaporation channel 115-288. The other three decay chains remain viable candidates for the 2n-evaporation channel 115-289.

  18. CD4+/CD25+T细胞与旋毛虫急性感染后大鼠的肠道免疫活化%The Study of CD 4 +/CD 25 +T Cell in the Pathogensis of Post-infectious Irritable Bowel Syndrome Induced By Acute Trichinella Infection

    Institute of Scientific and Technical Information of China (English)

    蔺蓉; 丁震; 马欢; 钱伟; 侯晓华

    2011-01-01

    Objective To investigate the change of blood Tregulatory cell ( Treg) after different time point of acute trichinella infection. Methods Male sprague-dawley rats were divided 4 groups in terms of sampling time;control group and PI-IBS group(2 weeks,4 weeks and 8 weeks after acute trichinella infection). Flow cytometry was used to detect the percent of Treg both in blood and laminal propria lymphocyte ( LPL). Results ( 1) The intestinal pathologic scores in 2 and 4 weeks groups are higher than that in control group;the scores in 8,12 weeks groups recover from the intestinal inflammation. (2)2 weeks after trichinella spirals infection,there is a significant decrease of CD 4 * CD 25 VCD 4 * both in peripheral blood and LPL, which is almost abolished in 8 weeks group. Conclusion There is declination of blood Treg and LPL-Treg percent after the early stage of acute trichinella infection,and this might involved in the pathogenesis of post-infections irritable bowel syndrome,%目的 研究不同时间点旋毛虫肠道急性感染后外周血及肠道黏膜内调节T细胞(CD 4+/CD 25+ Treg)的变化规律.方法 研究分为旋毛虫急性感染组(感染后2周,4周及8周)、对照组(与感染组相应年龄及饲养环境).测定肠道病理损伤程度,外周血中及肠道黏膜固有层淋巴细胞中CD 4 +/CD 25+T细胞占CD 4+淋巴细胞的百分比.结果 (1)模型动物感染后2周肠道各部位炎症评分明显高于正常组(回肠末端2.85±0.22,近端结肠2.66±0.27,远端结肠2.43±0.19,P<0.05);4周组炎症评分较2周组降低,但仍高于正常组;至感染后8周大致恢复正常.(2)感染2周后外周血Treg百分比明显下降(3.91±0.15 vs 2.28±0.13,P<0.01),下降比例41.7%.造模后4周,外周血Treg百分比仍低于正常对照组(3.91±0.15 vs 3.01±0.14,P<0.01).而至模型诱导成功的8周后,血Treg的比例(CD4+ CD25+/CD4+)趋于正常(3,48±0.15,0.01<P<0.05).(3)在急性旋毛虫感染2周后LPL- Treg

  19. Role of CD4+ CD25 + FoxP3 + Treg proportion in renal transplant recipients in evaluation of immune tolerance: a trans-vivo delayed type hypersensitivity assay%肾移植受者外周血中CD4+CD25+FoxP3+调节性T细胞比例在评价其免疫状态中的作用

    Institute of Scientific and Technical Information of China (English)

    韩容; 何跃; 刘宏; 吴雄飞

    2011-01-01

    目的 结合转移体内迟发超敏反应检测法初步探讨外周血中CD4+CD25+FoxP3+Treg的比例对亲体肾移植受者免疫状态评估的作用.方法 收集西南医院肾科门诊随访的2005-2008年间手术的亲体肾移植供者和受者各30例,进行转移体内迟发超敏反应检测(trans-vivo delayed type hypersensitivity-assay,Trans vivo-DTH)实验,根据实验结果将患者分为耐受组和排斥组;运用流式细胞技术检测2组中受者外周血单个核细胞(PBMCs)中CD4+CD25+FoxP3+Treg比例.结果 耐受组和排斥组裸鼠掌肿胀(同时注入受者PBMCs和供者抗原的脚掌)厚度分别为(1.72±0.44)×10-2、(8.05±2.26)×10-2mm,前者明显高于后者(P<0.05),2组受者外周血中CD4+CD25+FoxP3+Treg的比例分别为(9.23±1.79)%和(1.03±1.04)%,耐受组明显高于排斥组(P<0.05).耐受组和排斥组裸鼠脚掌皮下炎性水肿的厚度均与外周血中CD4+CD25+FoxP3+Treg的比例呈负相关(P<0.05,r分别为0.82 和0.87).结论 受者外周血中CD4+CD25+FoxP3+Treg的比例能够反应受者T细胞对供者抗原发生免疫反应的程度.外周血中CD4+CD25+FoxP3+Treg的比例在发现移植受者是否已有耐受方面有一定的参考价值.%Objective To investigate the role of the proportion of CD4 + CD25 + FoxP3 + Treg in peripheral blood in evaluating immune state of pro-kidney transplant recipients with the trans-vivo delayed type hypersensitivity (trans vivo-DTH) assay. Methods A total of 30 donors and their oorresponding recipients who received living related kidney transplantation during 2005 to 2008 in Southwest Hospital were randomly selected. All these recipients had sound transplantation and regular of follow-up. Trans vivo-DTH assay was used to divide the patients into tolerance group and rejection group. After the recipients' PBMCs and donors' antigen were injected into the footpads immunodeficient mice, the swelling was measured to evaluate the cellular immune response of the

  20. Change of CD4+CD25+Foxp3+Treg cells and Foxp3 expression in a mouse model of asthma and the effects of Icariin%哮喘小鼠CD4+CD25+Foxp3+调节T细胞和Foxp3蛋白的变化及淫羊藿苷干预作用

    Institute of Scientific and Technical Information of China (English)

    金华良; 董竞成; 罗清莉; 厉蓓; 吴金峰; 吕玉宝; 杜文静; 徐海林; 王根发; 王镓

    2012-01-01

    目的:研究哮喘小鼠CD4+CD25+Foxp3+调节T(Treg)细胞和Foxp3蛋白的变化,探讨淫羊藿苷对哮喘干预机制.方法:将BALB/c小鼠32只随机分为正常对照组、哮喘模型组、淫羊藿苷组、地塞米松阳性对照组,每组8只.哮喘模型制备用卵白蛋白(OVA)致敏大鼠并雾化吸入刺激,治疗组采用相应药物灌胃给药,对照组用等量生理盐水代替.最后一次激发24小时后,采用Buxco肺功能仪有创法检测小鼠气道反应性;HE染色评价观察小鼠肺组织病理形态学改变;流式细胞术检测脾脏CD4+CD25+Foxp3+Treg细胞比例及Foxp3蛋白表达量;免疫印迹法测定肺组织Foxp3蛋白表达量;ELISA法测定血清及肺泡灌洗液(BALF)IL-10水平.结果:与正常对照组比较:模型组气道阻力及气道炎症指数显著增加(P 0.05);脾Foxp3蛋白表达显著下降(P 0.05);与模型组比较:淫羊藿苷组气道阻力和气道炎症明显减轻(P 0.05),但淫羊藿苷可进一步上调哮喘小鼠肺组织Foxp3蛋白表达量(P 0.05). The expression of Foxp3 was significantly decreased in spleen, but was remarkably increased in lung tissues (P < 0. 05) . In addition, the level of IL-10 in serum of model group was significantly decreased ( P < 0. 05 ) . Icariin significantly attenuated airway hyperresponsiveness and inflammation, and further markedly enhanced expression of Foxp3 in lung tissues and IL-10 levels in serum, as compared lo OVA-exposed mice. Conclusion: The expression of Foxp3 protein is decreased within spleen CD4+ CD25 + Foxp3 + Treg cells in asthma. Icariin can increase the Foxp3 expression in lung tissue and levels of serum IL-10, which may contribute lo its antiaslhmalic effecls.

  1. BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2 analog, induces dose-dependent increases in CD25 expression and proliferation among unstimulated, human peripheral blood mononuclear cells in vitro.

    Science.gov (United States)

    Matthews, Lynn; Chapman, Sherita; Ramchandani, Meena S; Lane, H Clifford; Davey, Richard T; Sereti, Irini

    2004-12-01

    Interleukin-2 administration induces CD4 T cell expansion in HIV-infected patients, however, toxicity can limit dosing. BAY 50-4798 is a recombinant IL-2 analog with >1000-fold specificity for the high-affinity IL-2 receptor. The effects of this compound on unstimulated human PBMC were evaluated. PBMC from HIV(-) and HIV(+) donors were cultured in vitro with incremental doses of BAY 50-4798 or aldesleukin. CD25 expression and proliferation were evaluated with flow cytometry. Cytokine levels were measured by ELISA in culture supernatants. BAY 50-4798 induced dose-dependent increases in CD25 expression and proliferation of T cells, NK, and B cells and showed selectivity for CD4 T cells expressing CD25. Induction of pro-inflammatory cytokines was also dose-dependent and was observed at the concentrations of BAY 50-4798 with the highest biologic activity. These data suggest that BAY 50-4798 can induce proliferation of unstimulated T cells but loss of T cell selectivity and induction of pro-inflammatory cytokines occur at concentrations exerting the highest biologic activity. PMID:15507389

  2. 哮喘小鼠CD4+CD25+调节性T细胞数量及功能的改变%The change of the CD4+CD25+ regulatory T cells and its function in a mouse model of asthma

    Institute of Scientific and Technical Information of China (English)

    吴奎; 孙鲲; 毕玉田; 夏俊波; 王长征

    2005-01-01

    目的观察哮喘小鼠脾脏CD4+CD25+ 调节性T细胞(简称Treg细胞)数量及功能的改变.方法以屋尘螨提取液复制小鼠哮喘模型后,分离小鼠脾脏CD4+ T细胞,采用流式细胞仪检测Treg细胞占CD4+ T细胞的比例;分离Treg细胞,与屋尘螨提取液共同培养后测定上清液中白细胞介素-4(IL-4)及IL-10的含量;将Treg细胞与CD4+ T细胞共同培养,观察其对CD4+ T细胞增殖及IL-4、IL-5、γ-干扰素(IFN-γ)分泌的影响.结果哮喘小鼠脾脏Treg细胞占CD4+ T细胞比例明显下降;与正常组相比,哮喘小鼠脾脏Treg细胞IL-4、IL-10的分泌无明显差异;Treg细胞可显著抑制哮喘小鼠CD4+ T细胞的增殖,并降低其IL-4的分泌,对IFN-γ的合成分泌无明显作用;使用anti-CD25 mAb后,哮喘和正常小鼠Treg细胞的作用均被显著抑制.结论哮喘小鼠Treg细胞功能与正常对照组小鼠无明显区别,但数量显著下降.哮喘发病过程中Th2型反应占优势,与Treg细胞数量减少,对Th2型反应的抑制作用降低有一定关系.

  3. 胃癌患者外周血及癌组织中CD4+CD25+调节性T细胞、转录因子Foxp3的表达及临床意义%Expression and clinical signification of CD4+CD25+ regulatory T cells,the transcription factor Foxp3 in peripheral blood and cancerous tissue of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    陆威; 李永翔; 张尚鑫; 闫强

    2013-01-01

    目的 探讨胃癌患者外周血及胃癌组织中CD4+CD25+调节性T细胞(Tregs)和转录因子Foxp3表达及临床意义.方法 收集38例胃癌患者术前血液样本和20例健康体检者血液样本进行流式细胞仪检测,同时胃癌组中留取胃癌组织和癌旁组织(距肿瘤边缘>5 cm)进行免疫组化染色,检测CD4+CD25+Foxp3+Tregs表达,并与胃癌的TNM分期、肿瘤分化程度、淋巴转移、肿瘤所在部位、肿瘤直径等相关参数进行分析.结果 胃癌组外周血中CD4+CD25+Foxp3+Tregs的表达水平与对照组相比差异有统计学意义(P<0.01),且在胃癌TNM分期、淋巴转移组内比较差异有统计学意义(P<0.01).胃癌组织中Foxp3+Tregs的表达水平与癌旁组织相比,差异有统计学意义(P<0.01),且在胃癌TNM分期、分化程度、淋巴转移组内比较差异有统计学意义(P<0.01,P<0.05).外周血中CD4+CD25+ Foxp3+Tregs与胃癌组织中Foxp3+Tregs的表达水平呈显著正相关(r=0.786,P 5 cm ) from gastric cancer were subjected to immunohis-tochemistry to detect CD4 + CD25 + Foxp3 + Tregs expression, and the correlation analysis with some clinical related parameters was made. Results The percentages of CD4 + CD25 + Foxp3 + Tregs in peripheral blood of gastric cancer group were significantly higher than those from healthy control group( P <0. 01 ),and were highly correlated to TNM stage, lymph node metastases( P <0. 01 ). The percentages of Foxp3 + Tregs in gastric cancer tissue were significantly higher than those from para-tumorous tissue( P <0. 01 ),and were highly correlated to TNM stage,tumor differentiation,lymph node metastases( P < 0. 01 , P < 0. 05 ). The percentages of CD4 + CD25 + Foxp3 + Tregs in peripheral blood was positively correlated to Foxp3 + Tregs in gastric cancer tissue( r - 0. 786, P < 0. 01 ). Conclusion The proportion of CD4 + CD25 + Foxp3 + Tregs in Peripheral blood and Foxp3 + Tregs in gastric cancer tissue is significantly elevated in

  4. Molecular analysis of the human laminin alpha3a chain gene (LAMA3a): a strategy for mutation identification and DNA-based prenatal diagnosis in Herlitz junctional epidermolysis bullosa.

    Science.gov (United States)

    Pulkkinen, L; Cserhalmi-Friedman, P B; Tang, M; Ryan, M C; Uitto, J; Christiano, A M

    1998-09-01

    Mutations in the genes (LAMA3, LAMB3, and LAMC2) encoding the subunit polypeptides of the cutaneous basement membrane zone protein laminin 5 have been reported in different forms of junctional epidermolysis bullosa (JEB), an inherited blistering skin disease. In this study, we present the complete exon-intron organization of the "a" transcript of the laminin alpha3 chain gene, LAMA3a, which is expressed primarily in the skin. We have performed fine-resolution mapping of this gene on chromosome 18q11.2 using a human-hamster radiation hybrid panel. We have also developed a mutation-detection strategy based on the exon-intron structure of LAMA3a. This strategy, based on PCR amplification of genomic sequences, followed by heteroduplex scanning and automated nucleotide sequencing, was used for successful mutation screening in a family with the lethal (Herlitz) type of JEB, and two novel LAMA3 mutations were identified in the proband. The mutations consisted of a single-base pair deletion in LAMA3a exon A11 on the paternal allele, designated 1239delC, and a two-base pair deletion in LAMA3a exon A23 on the maternal allele, designated 2959delGG. This information was also used for DNA-based prenatal testing in a subsequent pregnancy in this family. Collectively, these results attest to our expanding capability to elucidate the genetic basis of various forms of epidermolysis bullosa using molecular techniques. PMID:9759651

  5. Salicylic acid binding of mitochondrial alpha-ketoglutarate dehydrogenase E2 affects mitochondrial oxidative phosphorylation and electron transport chain components and plays a role in basal defense against tobacco mosaic virus in tomato.

    Science.gov (United States)

    Liao, Yangwenke; Tian, Miaoying; Zhang, Huan; Li, Xin; Wang, Yu; Xia, Xiaojian; Zhou, Jie; Zhou, Yanhong; Yu, Jingquan; Shi, Kai; Klessig, Daniel F

    2015-02-01

    Salicylic acid (SA) plays a critical role in plant defense against pathogen invasion. SA-induced viral defense in plants is distinct from the pathways mediating bacterial and fungal defense and involves a specific pathway mediated by mitochondria; however, the underlying mechanisms remain largely unknown. The SA-binding activity of the recombinant tomato (Solanum lycopersicum) alpha-ketoglutarate dehydrogenase (Slα-kGDH) E2 subunit of the tricarboxylic acid (TCA) cycle was characterized. The biological role of this binding in plant defenses against tobacco mosaic virus (TMV) was further investigated via Slα-kGDH E2 silencing and transient overexpression in plants. Slα-kGDH E2 was found to bind SA in two independent assays. SA treatment, as well as Slα-kGDH E2 silencing, increased resistance to TMV. SA did not further enhance TMV defense in Slα-kGDH E2-silenced tomato plants but did reduce TMV susceptibility in Nicotiana benthamiana plants transiently overexpressing Slα-kGDH E2. Furthermore, Slα-kGDH E2-silencing-induced TMV resistance was fully blocked by bongkrekic acid application and alternative oxidase 1a silencing. These results indicated that binding by Slα-kGDH E2 of SA acts upstream of and affects the mitochondrial electron transport chain, which plays an important role in basal defense against TMV. The findings of this study help to elucidate the mechanisms of SA-induced viral defense.

  6. Buffett's Alpha

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

    Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

  7. 脐血CD4+CD25+CD127low调节T细胞及淋巴细胞亚群分析%Study on CD4+CD25+CD127low Regulatory T Cells and Lymphocytes Subsets in Umbilical Cord Blood

    Institute of Scientific and Technical Information of China (English)

    张劼; 陈军浩

    2012-01-01

    目的 检测新生儿脐带血淋巴细胞亚群和调节性T细胞比率,了解脐带血免疫学的特征.方法 使用Sysmex XE2100血细胞分析仪分别计数脐带血、新生儿母亲及对照组外周血淋巴细胞;采用流式细胞术分别检测其CD3+T细胞、CD19+B细胞、CD3- CD16+56+ NK细胞、CD3+ CD4+细胞、CD3+ CD8+细胞占淋巴细胞百分比,以及CD4+ CD25+CD127low调节性T细胞占CD4+细胞的百分比.结果 脐带血、新生儿母亲及对照组淋巴细胞计数分别为(3.68±1.07)×109/L,(1.42±0.44)×109/L和(2.06±0.88)×109/L;B淋巴细胞为:15.71%±3.89%,11.13%±3.79%和9.69%±2.22%;CD4+T细胞为:50.27%±9.08%,37.25%±7.13%和34.65%±7.17%;调节性T细胞为:6.94%±1.09%,5.09%±0.95%和4.8%1±0.99%.上述检测结果脐带血均显著高于母亲及对照组,P<0.01,母亲与对照组差异无统计学显著性意义P>0.05.三组间CD3+T细胞(69.64%±9.97%,74.83%±5.91%和69.41%±5.42%)和NK(11.36%±7.93%,10.48%±6.78%和16.31%±4.69%)细胞无显著性差异,P>0.05.脐带血中CD8+T细胞低于母亲及对照组(19.38%±6.62%,32.39%±2.08%和31.16%±1.87%),P<0.01.结论 脐血中高水平的CD4+ CD25+ CD127low调节性T细胞和低水平的CD8+T细胞有助于保持脐带血的低免疫状态.%Objective The proportions of lymphocytes subsets and regulatory T cells in umbilical cord blood were analyzed to explore the characteristic of umbilical cord blood in immunology. Methods To count lymphocytes by Sysmex XE2100 hema-tocyte cytometer. The percentages of CD3 + T cells,CD19+ B cells,CD3- CD16 + 56+ NK cells,CD3+ CD4+ cells,CD3+ CD8+ cells,and CD4+CD25+CD127low regulatory T cells among the umbilical cord bloods and the peripheral bloods from their mothers or control group were determined by flow cytometry. Results The quantity of lymphocytes in cord blood was significantly higher compared with mothers or with control group (3. 68

  8. Relationship between CD4 +CD25highFoxP3 +Treg and the rejection after stem cells transplant for ;Parkinson’s disease%CD4+CD25highFoxP3+Treg与帕金森病干细胞移植后排斥反应间的相关性研究

    Institute of Scientific and Technical Information of China (English)

    赵永波; 沈楠

    2013-01-01

    目的:通过应用骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)移植治疗帕金森病(Parkinson's disease,PD)大鼠,检测大鼠外周血中CD4+CD25highFoxP3+调节性T细胞(regulatory T cell,Treg)比例的变化及相关细胞因子的漂移,观察脑内免疫排斥反应的发生状况。以期探讨干细胞移植治疗PD后,外周血中Treg的改变与脑内免疫排斥反应间的相关性及其在干细胞移植后免疫耐受中的作用。方法 SD大鼠随机分为正常对照组、PD组、(PD+PBS)组、(PD+BMSCs)组。正常对照组大鼠不进行任何处理,为完全空白对照;余下大鼠均通过脑内立体定向注射6-羟基多巴胺(6-hydmxydopamine,6-OHDA)建立PD大鼠模型。成功建模后第3周,(PD+PBS)组大鼠脑内定向注射PBS缓冲液;(PD+BMSCs)组大鼠脑内定向注射应用全骨髓贴壁法培养的大鼠BMSCs悬液;PD组大鼠不做任何处理。PBS缓冲液和BMSCs悬液注射2周后,各组大鼠均应用流式细胞术(lfow cytometry,FCM)检测其外周血中CD4+CD25highFoxP3+Treg占T淋巴细胞比例的变化,并运用酶联免疫吸附测定(ELISA)检测外周血中白介素(IL)-4、IL-10和干扰素-γ(INF-γ)等相关细胞因子的改变。另外,通过免疫组织化学染色法观察大鼠脑内酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性神经元、离子钙接头蛋白分子-1(ionized calcium bindingadaptor molecule-1, iba-1)阳性细胞、主要组织相容性复合体-Ⅱ(major histocompatibility complex-Ⅱ,MHC-Ⅱ)分子的变化。同时,(PD+BMSCs)组大鼠采用EdU染色法监测移植后BMSCs的存活情况。结果脑内立体定向注射6-OHDA 3周后,部分大鼠腹腔注射阿扑吗啡可诱导出旋转行为,表现为向健侧旋转,呈首尾相接状,以210圈/30分钟为标准,建模成功率达65.45%,并且免疫组织化学染色显

  9. Alpha fetoprotein

    Science.gov (United States)

    Fetal alpha globulin; AFP ... Greater than normal levels of AFP may be due to: Cancer in testes , ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer ...

  10. 白细胞降低性肺炎患者 CD4+CD25+调节性T 细胞的表达与临床意义%Expression and signifiacnce of CD4 +CD25 +regulatory T cells(Treg) in the pathogenesis for the pneumonia patients with leucopenia

    Institute of Scientific and Technical Information of China (English)

    林燕梅

    2015-01-01

    目的:探索CD4+CD25+调节性T细胞( Treg)在白细胞( WBC)降低性肺炎( LP)中的表达及临床意义。方法对40例LP患者进行血常规及Treg检测和痰培养,将Treg与WBC及病原体类型进行相关性分析。结果 LP组患者 Treg、WBC 及单核细胞( MON )均明显降低( P<0.05)。痰培养显示肺炎支原体( MP)占26例并均予阿奇霉素治疗,发现第3天Treg频率显著高于第1天( P=0.028)。 Treg与WBC及MON比例均呈正相关性( P<0.05),但与中性粒细胞及淋巴细胞均呈负相关性( P<0.05);Treg与MP感染存在显著负相关性( P<0.05)。结论 Treg频率降低是LP的重要免疫表现,有助于支原体肺炎的早期诊断及疗效判断。%Objective To explore the expression and significance of CD 4 +CD25 +regulatory T cells ( Treg) for the patients with leucopenia pneumonia ( LP) .Methods Forty patients with LP were enrolled and their blood rou -tine examination ,Treg testing and sputum cultivation were done .The correlations between Treg ,white blood cell ( WBC) and pathogens were analyzed .Results Compared with the control group , Treg, WBC and monocytes (MON) decreased significantly(P<0.05).Sputum cultivation showed that there were 26 patients suffering from my-coplasma(MP) infection and they were all treated with azithromycin .The frequencies of Treg on the 3rd day of the MP patients were significantly higher than those on the 1st day during azithromycin treatment (P=0.028).Correlation a-nalysis showed that Treg was positively related to WBC and MON ( P<0.05 ) , whereas Treg was negatively related to neutrophil granulocyte and lymphocyte , as well as the MP ( P<0.05 ) .Conclusion Decreasing of Treg is one of the important immunological features for patients with LP , which can help the early diagnosis and curative effect evalua-tion for the MP.

  11. Change of CD4+ CD25+ CD127 low regulatory T cells in peripheral blood of patients with Graves disease treated by 131 I or antithyroid drugs therapy%Graves病131I或抗甲状腺药物治疗前后外周血CD4+CD25+CD127low调节性T细胞的变化

    Institute of Scientific and Technical Information of China (English)

    杨静; 潘天荣; 杜益君; 钟兴

    2016-01-01

    目的:探讨调节性T细胞( Treg)在Graves病( GD)患者外周血中变化,以及131 I或抗甲状腺药物( ATD)治疗后其变化趋势,寻找评价131 I和ATD治疗疗效的新指标。方法健康者40例设为对照组,初诊GD患者40例设为GD组,并将GD组随机分成131 I 治疗组(20例)及 ATD 治疗组(20例)。检测131 I治疗组、ATD治疗组治疗前、治疗后及对照组CD4+CD25+CD127 low Treg 比例、白介素-10( IL-10)、转化生长因子-β1(TGF-β1)水平,通过统计学软件处理相关结果。结果①治疗前GD组Treg比例较对照组明显降低,差异有统计学意义( P<0.01);②131 I治疗组、ATD治疗组治疗后第3个月及第6个月Treg比例较治疗前均升高,差异均有统计学意义( P <0.01);③治疗后第3个月及第6个月, ATD治疗组Treg比例与131 I治疗组差异无统计学意义;④治疗前GD组IL-10、TGF-β1水平较对照组均降低,治疗后6个月,细胞因子水平较治疗前均升高,差异均有统计学意义(P<0.05),各时间点131 I治疗组与ATD治疗组之间,细胞因子差异无统计学意义。结论 GD患者Treg比例和功能显著降低,治疗后部分恢复,因此,对于甲亢患者,Treg可能是评价免疫状态及治疗后病情缓解的指标之一。%Objective To investigate the changes of regulatory T cells ( Treg) in Graves disease ( GD) before and after being treated by 131 I or antithyroid drugs( ATD) ,and to seek for new clinical indicators to evaluate the treat-ment response. Methods The study groups included 40 patients with GD ( GD group) , 20 of whom were treated by 131 I ,others were treated by ATD. Forty healthy donors without history of thyroid or autoimmune disease were en-rolled in control group. The proportions of CD4 +CD25 +CD127low Treg , IL-10 and TGF-β1 were tested before and after treatment respectively. Results ① The significant decrease in the proportion of CD4 +CD25 +CD127low Treg cells in untreated GD patients ( GD group) was

  12. Inhibitory effect of CD4~+CD25~+CCR6~+ regulatory T cells against CD8~+T cells in mouse mammary carcinoma model%CD4~+CD25~+CCR6~+调节性T细胞在小鼠乳腺癌模型中对CD8~+T细胞的抑制作用

    Institute of Scientific and Technical Information of China (English)

    徐林; 徐薇; 蒋正刚; 熊思东

    2009-01-01

    Objective:To observe the inhibitory effect of CD4~+CD25~+CCR6~+ regulatory T cells (CCR6~+ Tregs) against CD8~+T cells in vivo, and to investigate its relationship with tumor immune escape. Methods: Mouse mammary carcinoma models were established by inoculating mammary carcinoma 4T1 cells into nude mice. CCR6~+ Tregs were isolated by FACS, and the Foxp3 expression on CCR6~+ Tregs was further analyzed by FACS. 4T1 specific CD8~+T cells were labeled with CFSE after isolation by FACS, and then transferred into 4T1 bearing nude mice combined with or without CCR6~+ Tregs or CD4~+CD25~+CCR6-regulatory T cells (CCR6- Tregs). Tumor growth and survival of 4T1 bearing mice were observed. The proliferation, IFN-γ production, and granzyme B expression of CD8~+T cells were examined by FACS. Results: Both CCR6~+ Tregs and CCR6- Tregs expressed high levels of Foxp3. The tumors in CCR6~+ Tregs and CD8~+T cells co-transferred mice grew faster than those in CCR6- Tregs co-transferred and CD8~+T cell-transferred groups. The survival period of 4T1 bearing mice was significantly decreased in CCR6~+ Tregs co-transferred group (P<0.05). Furthermore, the proliferation, IFN-γ production and granzyme B expression of CD8~+ T cells were also dramatically decreased in CCR6~+ Tregs co-transferred group compared with those in CCR6- Tregs co-transferred and CD8~+ T cell-transferred groups (P<0.05). Conclusion: CCR6~+ Tregs can effectively inhibit the function of CD8~+ T cells, which might play an important role in tumor immune escape, tumor development and progress.%目的:观察CD4~+CD25~+CCR6~+调节性T细胞(简称CCR6~+Tregs)体内对CD8~+T细胞功能的抑制作用,并探讨其与肿瘤免疫逃逸的关系.方法:建立4T1乳腺癌细胞荷瘤裸鼠模型,FACS分选CCR6~+Tregs,检测其Foxp3的表达;FACS分选4T1特异性CD8~+T细胞,CFSE标记后分别与CCR6~+Tregs或CCR6-Tregs共同过继转输入4T1荷瘤裸鼠体内,观察荷瘤裸鼠肿瘤生长情况和小鼠存活

  13. Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4+CD25+ regulatory T cells

    International Nuclear Information System (INIS)

    Highlights: ► This is the first study to provide direct evidence of the role of Stat5b in NOD mice. ► Over-expression of wild type Stat5b transgene protects NOD mice against diabetes. ► This protection may be mediated by the up-regulation of CD4+CD25+ Tregs. -- Abstract: The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4+ T cells and especially CD8+ T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4+ and CD8+ T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-γ, TNF-α and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4+CD25+ regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4+CD25+ regulatory T cells.

  14. Fermented fish oil suppresses T helper 1/2 cell response in a mouse model of atopic dermatitis via generation of CD4+CD25+Foxp3+ T cells

    Directory of Open Access Journals (Sweden)

    Han Sang-Chul

    2012-08-01

    Full Text Available Abstract Background Allergic skin inflammation such as atopic dermatitis (AD, which is characterized by pruritus and inflammation, is regulated partly through the activity of regulatory T cells (Tregs. Tregs play key roles in the immune response by preventing or suppressing the differentiation, proliferation and function of various immune cells, including CD4+ T cells. Recent studies report that fermentation has a tremendous capacity to transform chemical structures or create new substances, and the omega-3 polyunsaturated fatty acids (n-3 PUFAs in fish oil can reduce inflammation in allergic patients. The beneficial effects of natural fish oil (NFO have been described in many diseases, but the mechanism by which fermented fish oil (FFO modulates the immune system and the allergic response is poorly understood. In this study, we produced FFO and tested its ability to suppress the allergic inflammatory response and to activate CD4+CD25+Foxp3+ Tregs. Results The ability of FFO and NFO to modulate the immune system was investigated using a mouse model of AD. Administration of FFO or NFO in the drinking water alleviated the allergic inflammation in the skin, and FFO was more effective than NFO. FFO treatment did increase the expression of the immune-suppressive cytokines TGF-β and IL-10. In addition, ingestion of FFO increased Foxp3 expression and the number of CD4+CD25+Foxp3+ Tregs compared with NFO. Conclusions These results suggest that the anti-allergic effect of FFO is associated with enrichment of CD4+CD25+ Foxp3+ T cells at the inflamed sites and that FFO may be effective in treating the allergic symptoms of AD.

  15. Alpha particle emitters in medicine

    International Nuclear Information System (INIS)

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 (211At) and natural bismuth-212 (212Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 (223Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs

  16. Alpha particle emitters in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R.

    1989-09-01

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ({sup 211}At) and natural bismuth-212 ({sup 212}Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ({sup 223}Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs.

  17. 合作小型猪 T 细胞受体α链的基因结构及其多样性%Genetic structure and diversity of T cell receptor alpha chain genes in Hezuo minipig

    Institute of Scientific and Technical Information of China (English)

    高建平; 李玩生; 曾爽; 房永祥; 冯海燕; 杨孝朴; 景志忠

    2014-01-01

    Objective To analyze the complexity of molecular structure in porcine T cell receptor gene and its similarity compared to humans.Method Based on the gene of porcine T cell receptor alpha chain ( TCRα) from the Gen-Bank database, 93 swine T cell receptor alpha chain genes ( STA) were cloned by reverse transcription-polymerase chain reaction (RT-PCR) from porcine peripheral blood lymphocytes, lymph nodes and spleen.Result Sequence analysis showed that STA genes all contain a domain of variable signal peptide and V, hypervariable J and conservative C.Howev-er, nucleotide sequence of STA was not completely identical with only 68.4%to 98.7%homology among genes, and had extremely sophisticated polymorphism and diversity.This was accord with the genetic structure of TCRαchain.Molecular structure, genetic evolution and classification of these genes were carried out according to the homology of TCRαgene, which all have several sites and zones of mutation on the domain of signal peptide, FR1 and CDR1, FR2 and CDR2, FR3 and CDR3.Analysis of similarity and classification of TCRαV domain(STAV)and J domain (STAJ) of Hezuo minipig u-sing IMGT/V-QUEST tools compared with those of humans found the genetic evolution relationship that was closer, and each of TRAV and TRAJ also found to have a corresponding fragment of humans, ever in 92% of similarity of TRAV be-tween swine and humans.Conclusion Our results indicate that inbred Hezuo minipig possesses genetic diversity against complicated environment of microbes in healthy status, and Hezuo minipig is suitable as an animal model for research on human immunology and diseases.%目的:探讨猪TCR基因分子结构的复杂性及其与人类的相似性。方法以公开的猪TCRα链基因为参考序列设计两对特异性引物,用RT-PCR法从合作小型猪外周血、淋巴结和脾脏的淋巴细胞中克隆了93个猪TCRα基因(简称STA)。结果测序分析表明,克隆的猪TCRα链的基因均含有可变

  18. A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW)).

    NARCIS (Netherlands)

    Phylipsen, M.; Vogelaar, I.P.; Schaap, R.A.; Arkesteijn, S.G.; Boxma, G.L.; Helden, W.C. van; Wildschut, I.C.; Bruin-Roest, A.C. de; Giordano, P.C.; Harteveld, C.L.

    2010-01-01

    Alpha-thalassemia is an inherited hemoglobin disorder characterized by a microcytic hypochromic anemia caused by a quantitative reduction of the alpha-globin chain. The majority of the alpha-thalassemias is caused by deletions in the alpha-globin gene cluster. A deletion in the alpha-globin gene clu

  19. Increase of circulating CD4+CD25highFoxp3+ regulatory T cells in patients with metastatic renal cell carcinoma during treatment with dendritic cell vaccination and low-dose interleukin-2

    DEFF Research Database (Denmark)

    Berntsen, Annika; Brimnes, Marie Klinge; thor Straten, Per;

    2010-01-01

    Regulatory T cells (Treg) play an important role in the maintenance of immune tolerance and may be one of the obstacles of successful tumor immunotherapy. In this study, we analyzed the impact of administration of dendritic cell (DC) vaccination in combination with low-dose interleukin (IL)-2 in...... patients with metastatic renal cell carcinoma on the frequency of CD4+CD25highFoxp3+ Treg cells in peripheral blood. We found that the treatment increased the frequency of Treg cells more than 7-fold compared with pretreatment levels (P...

  20. Human Adipose-Derived Stromal/Stem Cells Induce Functional CD4+CD25+FoxP3+CD127− Regulatory T Cells Under Low Oxygen Culture Conditions

    OpenAIRE

    Frazier, Trivia P.; McLachlan, James B.; Gimble, Jeffrey M.; Tucker, Hugh A; Brian G Rowan

    2014-01-01

    Human adipose tissue stromal/stem cells (ASCs) are known to induce proliferation of resting T cells under ambient (21%) O2 conditions; however, ASCs exist physiologically under lower oxygen (5% O2) conditions in adipose tissue. The effects of low oxygen levels on ASC immunomodulation of T cells are unknown. In this study, we show that ASCs stimulated proliferation of naive CD4+ T cells and the percentage of CD25+ T cells was significantly increased under both low and ambient O2. Forkhead box ...

  1. Expressions of folkhead helix transcription factor 3 on CD4+ CD25+ regulatory T lymphocyte in intestinal mucosa in human immunodeficiency virus infected patients%人类免疫缺陷病毒感染者肠黏膜组织中CD4+CD25+调节性T淋巴细胞及叉头状转录因子3的表达

    Institute of Scientific and Technical Information of China (English)

    孙磊; 兰孟东; 郎振为; 王鹏; 李坪; 赵红心; 滕晓英; 周新刚; 张亮; 沈冰

    2011-01-01

    Objective To investigate the changes of CD4+ CD25+ regulatory T lymphocyte (Treg) and expressions of folkhead helix transcription factor 3 (FoxP3) in intestinal mucosa in human immunodeficiency virus (HIV) infected patients. Methods Twenty-one HIV infected patients and 17 control subjects without HIV infection were included in this study. The expression of FoxP3, which was considered as a specific marker of CD4+ CD25 + Treg, was detected in intestinal mucosa specimens from HIV infected patients by immunohistochemistry. Meanwhile, the in situ expression of CD4+ T lymphocyte was also determined by immunohistochemistry. The data were analyzed by t test. Results The positive labeling index of CD4+ T lymphocyte in intestinal mucosa was significantly lower in HIV infected patients compared to the controls (11. 56%±4. 44% vs 43. 49% ±8. 90% ,t=-11. 86,P<0. 01). The positive labeling index of FoxP3 in intestinal mucosa was also significantly lower in HIV infected patients compared to the controls (0.46% ± 0.20% vs 1. 18% ± 0. 44% ,t= - 5. 98,P<0.01). Conclusion The depletion of CD4+ CD25+ Treg is accompanied with the depletion of CD4 + T lymphocyte and the reduction of FoxP3 expression in intestinal mucosa of HIV infected patients.%目的 研究HIV感染者肠黏膜组织中CD4+CD25+调节性T淋巴细胞(Treg)及叉头状转录因子3(FoxP3)的表达.方法 应用免疫组织化学法,检测21例HIV感染者及17例非HIV感染者肠黏膜组织中CD4+CD25+Treg的特异性标志物FoxP3的表达以及CD4+T淋巴细胞的原位表达.数据处理应用t检验.结果 HIV感染者肠黏膜组织中CD4+T淋巴细胞阳性标记指数为11.56%±4.44%,显著低于非HIV感染者的43.49%±8.90%(t=-11.86,P<0.01).HIV感染者肠黏膜组织中FoxP3阳性标记指数为0.46%±0.20%,显著低于非HIV感染者的1.18%±0.44%(t=-5.98,P<0.01).结论 HIV感染者肠黏膜组织中CD4+T淋巴细胞出现消减,CD4+CD25+Treg也出现消减,FoxP3表达下降.

  2. 激素抵抗性哮喘患者外周血CD4+CD25+Foxp3+调节性T细胞及白细胞介素10、转化生长因子β1水平变化及其临床意义%The clinical significance of CD4+ CD25+ Foxp3+ regulatory T cell and interleukin-10,transforming growth factor-β1 in patients with steroid-resistant asthma

    Institute of Scientific and Technical Information of China (English)

    王善飞; 赵平; 许庆元

    2013-01-01

    目的 研究激素抵抗性哮喘(SRA)患者外周血CD4+ CD25+ Foxp3+调节性T细胞(Treg)及白细胞介素10(IL-10)、转化生长因子β1(TGF-β1)水平变化及其临床意义.方法 选取哮喘患者79例,分为SRA组(31例)和激素敏感性哮喘(SSA)组(48例).同时选取健康体检者45例作为对照组,采用流式细胞术检测CD4+ CD25+Foxp3+ Treg的表达水平,酶联免疫吸附法检测血清IL-10和TGF-β1水平.结果 SRA组和SSA组CD4+ CD25+ Foxp3+ Treg在CD4+T细胞中的比例和绝对值分别为0.0225±0.0063、(1.09±0.23)×107/L和0.0345±0.0094、(1.35±0.14)×107/L,均较对照组[0.0537±0.0128、(2.06±0.27)×107/L]明显下降,且SRA组的下降程度更加明显,差异均有统计学意义(P<0.05).SRA组和SSA组血清TGF-β1水平均较对照组明显下降[(138.12±23.26)、(176.25±40.37) ng/L比(281.22±47.15) ng/L],差异有统计学意义(P<0.05).SRA组血清IL-10水平较对照组明显下降[(516.43±86.33) ng/L比(763.02±90.19) ng/L],差异有统计学意义(P<0.05).而SSA组血清IL-10水平与对照组比较差异无统计学意义(P> 0.05).SRA组血清IL-10和TGF-β1水平均较SSA组明显下降,差异有统计学意义(P<0.05).SRA组和SSA组血清IL-10和TGF-β1水平与CD4+ CD25+ Foxp3+ Treg水平呈明显正相关(P<0.01).结论 CD4+ CD25+ Foxp3+ Treg、IL-10和TGF-β1之间的相互作用在SRA的发生、发展中发挥了重要作用,而通过增加外周血CD4+ CD25+Foxp3+ Treg数量,稳定其功能,增加IL-10和TGF-β1表达,可能是治疗SRA的重要途径.%Objective To study the clinical significance of CD4 + CD25+ Foxp3 + regulatory T cell (Treg) and interleukin 10 (IL-10),transforming growth factor-β1 (TGF-β 1) in patients with steroidresistant asthma (SRA).Methods Seventy-nine patients with asthma were divided into SRA group (31cases) and steroid-sensitive (SSA) group (48 cases).Forty-five healthy subjects were selected simultaneously as control group.CD4+ CD25+ Foxp3 +Treg level

  3. Dipole oscillation modes in $\\alpha$-clustering light nuclei

    CERN Document Server

    He, W B; Cao, X G; Cai, X Z; Zhang, G Q

    2016-01-01

    The alpha cluster states are discussed in an extended quantum molecular dynamics (EQMD) model frame. Different alpha cluster structures are studied in details, such as $^8$Be two-alpha cluster structure, $^{12}$C triangle structure, $^{12}$C chain structure, $^{16}$O chain structure, $^{16}$O kite structure, and $^{16}$O square structure. The properties like width of wave packets for different alpha clusters, momentum distribution, and the binding energy among alpha clusters are studied. It is also discussed how the $\\alpha$ cluster degree of freedom affects nuclear collective vibrations. The different $\\alpha$ cluster configurations in $^{12}$C and $^{16}$O have corresponding characteristic spectra of GDR and the coherence of different alpha clusters's dipole oscillation are described in details. The number and centroid energies of peaks in the GDR spectra can be reasonably explained by the geometrical and dynamical symmetries of $\\alpha$-clustering configurations. The GDR can be regarded as a very effective...

  4. An Imbalance between Frequency of CD4+CD25+FOXP3+ Regulatory T Cells and CCR4+ and CCR9+ Circulating Helper T Cells Is Associated with Active Perennial Allergic Conjunctivitis

    Directory of Open Access Journals (Sweden)

    J. Galicia-Carreón

    2013-01-01

    Full Text Available Allergic conjunctivitis (AC is one of the most common eye disorders in ophthalmology. In mice models, it has been suggested that control of allergic conjunctivitis is a delicate balance between Tregs and inflammatory migrating effector cells. Our aim was to evaluate the frequency of Tregs and the frequency of homing receptors expressing cells in peripheral blood mononuclear cells (PBMC from patients with perennial allergic conjunctivitis (PAC. The analyses of phenotypic markers on CD4+ T cells and both soluble or intracellular cytokines were performed by flow cytometry. CD4+CD25+ cells were 15 times more frequent in PBMC from patients than HC; the vast majority of these CD4+CD25+ cells were FOXP3−, and most of CD4+ T cells were CCR4+ and CCR9+ cells. Upon allergen-stimulation, no significant changes were observed in frequency of Treg; however, an increased frequency of CD4+CCR4+CCR9+ cells, CD4+CD103+ cells and CD4+CD108+ cells with increased IL-5, IL-6, and IL-8 production was observed. These findings suggest an immune dysregulation in PAC, characterized by diminished frequency of Tregs and increased frequency of circulating activated CD4+ T cells; upon allergen-stimulation, these cells were expressing cell-surface molecules related to mucosa homing and were able to trigger an inflammatory microenvironment.

  5. Protective Effect of CXCR3⁺CD4⁺CD25⁺Foxp3⁺ Regulatory T Cells in Renal Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Jun, Cao; Qingshu, Li; Ke, Wei; Ping, Li; Jun, Dong; Jie, Luo; Su, Min

    2015-01-01

    Regulatory T cells (Tregs) suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI) is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61) + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb) to deplete Tregs before renal ischemia. CD4(+)CD25(+)Foxp3(+) Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN), serum creatinine (Scr) levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.

  6. CD4+CD25+调节性T细胞在自身免疫性溶血性贫血患者中的变化及意义%Change and significance of CD4+CD25+ regulatory T cells in patients with autoimmune hemolytic anemia

    Institute of Scientific and Technical Information of China (English)

    黄东平; 何合胜

    2014-01-01

    Objective To investigate the change of regulatory T-cells (Treg) before and after therapy in patients with autoimmune hemolytic anemia (AIHA),and to study the role of Treg in AIHA.Methods Treg cells numbers was measured by flow cytometry.Results Before treatment,Treg cells in AIHA patients was (1.32 ± 0.87) %,which was significantly lower than (3.08 ± 0.96) % in the controls (t =-5.37,P < 0.01).After treatment,Treg cells in AIHA patients was significantly increased [(4.96 ± 1.13)%] (t =-16.94,P <0.01).Conclusion Treg cells decreased in AIHA patients.Glucocorticoid might play a role in AIHA treatment by up-regulating Treg cells number.%目的 探讨CD4+CD25+Foxp3+调节性T细胞(Treg)在自身免疫性溶血性贫血(AIHA)患者中的变化.方法 应用流式细胞术检测AIHA患者治疗前后外周血Treg的数量变化.结果 AIHA患者治疗前外周血中Treg细胞比例为(1.32±0.87)%,明显低于对照组(3.08±0.96)%(t=-5.37,P<0.01).治疗后Treg细胞比例为(4.96±1.13)%,明显高于治疗前(t=-16.94,P<0.01),且高于对照组(t=-4.96,P<0.01).结论 AIHA患者中Treg细胞数量下降,糖皮质激素通过上调Treg细胞数量可以控制自身免疫性溶血性贫血.

  7. CD4+CD25+ Treg cell and Foxp3 expression play key roles in the pathogenesis of cervical carcinoma%宫颈癌患者外周血CD4+CD25+调节性T细胞及其Foxp3表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    徐华; 王丹波

    2015-01-01

    目的 评价宫颈癌患者外周血CD4+CD25+调节性T细胞(Regulatery T cell,Treg)及其Foxp3表达的临床意义.方法 收集中国医科大学附属盛京医院自2012年1月至2013年6月手术治疗的早期宫颈癌患者(FIGO分期≤Ⅱ期)34例,高级别宫颈上皮内瘤变(CIN2/3)患者30例以及20例健康女性作为正常对照.流式细胞技术检测各研究组手术前、后及对照组外周血Treg及Foxp3+ Treg细胞占CD4+T细胞比例,应用t检验和单因素方差法进行统计学分析.结果 比较宫颈癌、CIN2/3及对照组外周血Treg及Foxp3+ Treg细胞所占CD4+T细胞比例,各组间差异有统计学意义(P<0.05);术后早期(7 d),宫颈癌及CIN2/3患者外周血Foxp3+ Treg细胞所占比例较术前显著下降(P<0.05),但Treg细胞所占比例无显著性变化(P>0.05);术后恢复期(1个月),宫颈癌及CIN2/3患者外周血Foxp3+ Treg细胞所占比例较术后早期无显著变化,但Treg细胞所占比例较术后早期显著性降低(P<0.05).结论 宫颈癌患者外周血Treg细胞及其Foxp3的表达均与病变程度相关;Treg细胞Foxp3的表达具有不稳定性;宫颈癌肿瘤微环境可能是维持Treg细胞分化增殖及Foxp3稳定表达的外在客观条件.

  8. The Alpha-Melanocyte Stimulating Hormone Induces Conversion of Effector T Cells into Treg Cells

    Directory of Open Access Journals (Sweden)

    Andrew W. Taylor

    2011-01-01

    Full Text Available The neuropeptide alpha-melanocyte stimulating hormone (α-MSH has an important role in modulating immunity and homeostasis. The production of IFN-γ by effector T cells is suppressed by α-MSH, while TGF-β production is promoted in the same cells. Such α-MSH-treated T cells have immune regulatory activity and suppress hypersensitivity, autoimmune diseases, and graft rejection. Previous characterizations of the α-MSH-induced Treg cells showed that the cells are CD4+ T cells expressing the same levels of CD25 as effector T cells. Therefore, we further analyzed the α-MSH-induced Treg cells for expression of effector and regulatory T-cell markers. Also, we examined the potential for α-MSH-induced Treg cells to be from the effector T-cell population. We found that the α-MSH-induced Treg cells are CD25+  CD4+ T cells that share similar surface markers as effector T cells, except that they express on their surface LAP. Also, the α-MSH treatment augments FoxP3 message in the effector T cells, and α-MSH induction of regulatory activity was limited to the effector CD25+ T-cell population. Therefore, α-MSH converts effector T cells into Treg cells, which suppress immunity targeting specific antigens and tissues.

  9. $\\alpha_s$ review (2016)

    CERN Document Server

    d'Enterria, David

    2016-01-01

    The current world-average of the strong coupling at the Z pole mass, $\\alpha_s(m^2_{Z}) = 0.1181 \\pm 0.0013$, is obtained from a comparison of perturbative QCD calculations computed, at least, at next-to-next-to-leading-order accuracy, to a set of 6 groups of experimental observables: (i) lattice QCD "data", (ii) $\\tau$ hadronic decays, (iii) proton structure functions, (iv) event shapes and jet rates in $e^+e^-$ collisions, (v) Z boson hadronic decays, and (vi) top-quark cross sections in p-p collisions. In addition, at least 8 other $\\alpha_s$ extractions, usually with a lower level of theoretical and/or experimental precision today, have been proposed: pion, $\\Upsilon$, W hadronic decays; soft and hard fragmentation functions; jets cross sections in pp, e-p and $\\gamma$-p collisions; and photon F$_2$ structure function in $\\gamma\\,\\gamma$ collisions. These 14 $\\alpha_s$ determinations are reviewed, and the perspectives of reduction of their present uncertainties are discussed.

  10. In-vitro characterization of novel and functional regulatory SNPs in the promoter region of IL2 and IL2R alpha in a Gabonese population

    OpenAIRE

    Huang Xiangsheng; Kühne Vera; Kun Jürgen F J; Soboslay Peter T; Lell Bertrand; TP, Velavan

    2012-01-01

    Abstract Background The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism. Methods We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25) in Gabonese individuals exposed to plentiful parasitic infections. Results We...

  11. 全身照射预处理供体对异基因大鼠肝移植的作用及对受体内CD4~+CD25~+调节性T细胞的影响%Total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the effects on CD4~+ CD25~+ regulatory T cells content

    Institute of Scientific and Technical Information of China (English)

    张业伟; 严栋梁; 卢思聪; 王学浩; 刘允怡

    2009-01-01

    Objective To study the effect of total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the role of CD4~+ CD25~+ regulatory T cells on induction of immunotolerance in the recipient.Methods Liver transplantation was performed using male Lewis rats as donors and male DA rats as recipients.These rata were randomly allocated into the following groups:Control group,Homogeneity Liver Transplantation group,Idio-immunotolerance group and Acute Rejection group.After transplantation,survival time rate of each group were observed.Serum ALT,TB level,Foxp3~+ CD4~+ CD25~+ regulatory T cells,expression of GITR on T cell subgroup,histopathology of the hepatic graft on day 14,spleen CTL lytic activity on day 14 were measured.Results In the ldio-immnunotolerance group,the recipients suffered from transient rejection after surgery but acquired immunotolerance and survived long.In the Acute Rejection group,the donors were preconditioned with total body irradiation before liver transplantation.All recipients died between day 17 to 21.Serum ALT and TB increased significantly and the ratio of Foxp3~+ CD4~+ CD25~+ regulatory T cells decreased significantly compared with the Idioimmunotolerance group,the Homogeneity Liver Transplantation group and the Control group.The expression of GITR on CD3~+ CD4~+ T cells in the peripheral blood decreased.the expression of GITR on CD3~+ CD8~+ T cells and CTL lytic activity of the recipients increased by preconditioning of the donors with total body irradiation.Conclusions Preconditioning of the donors with total body irradiation eliminated the passenger lymphocytes of the liver graft,decreased the expression of Foxp3~+ CD4~+ CD25~+ regulatory T cells in peripheral blood,and increased the expression of GITR on CD3~+ CD8~+ T cells,thus affected the course of tolerance and induced acute rejection after liver transplantation.%目的 探讨全身照射(TBI)预处理诱导大鼠肝移植术后急性排

  12. IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

    Science.gov (United States)

    Alcina, Antonio; Fedetz, María; Ndagire, Dorothy; Fernández, Oscar; Leyva, Laura; Guerrero, Miguel; Abad-Grau, María M.; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla

    2009-01-01

    Background IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. Methods and Results Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. Conclusions These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases. PMID:19125193

  13. 呼吸道合胞病毒毛细支气管炎患儿外周血CD4+CD25+调节性T细胞与Th17细胞功能变化及意义%Changes and the clinical significance of CD4+ CD25+ regulatory T cells and Th17 cells in peripheral blood of infants with respiratory syncytial virus bronchiolitis

    Institute of Scientific and Technical Information of China (English)

    李宾; 吴福玲; 冯学斌; 孙大康; 崔晴晴; 赵志旭

    2012-01-01

    AIM: To observe the percentages of CD4 + CD25+ regulatory T cells (Tregs) and Thl7 cells and the levels of IL-10, TGF-p and IL-17 in peripheral blood of infants with respiratory syncytial virus ( RSV) bronchiolitis. The relationship between above cells, cytokines and RSV bronchiolitis was determined. METHODS: Thirty-three infants with RSV bronchiolitis, twenty-eight infants with non-RSV pneumonia and twenty-six healthy infants were enrolled. The percentages of Tregs and Thl7 cells in peripheral blood were detected by flow cytometer (FCM), and the levels of IL-10, TGF-pand IL-17 in plasma were determined by ELISA. RESULTS: The percentage of Tregs and the levels of IL-10 and TGF-pin infants with RSV bronchiolitis were significantly lower than those in infants with non-RSV pneumonia and healthy infants ( P < 0. 05), while the percentage of Thl7 cells and the level of IL-17 in infants with RSV bronchiolitis were significantly higher than those in infants with non-RSV pneumonia and healthy infants ( P < 0. 05). CONCLUSION: The imbalance between Tregs and Thl7 cells in peripheral blood of infants with RSV bronchiolitis may be one of the pathogenesis of RSV bronchiolitis.%目的:探讨呼吸道合胞病毒(RSV)毛细支气管炎患儿外周血CD4+ CD25+调节性T细胞和Th17细胞及其分泌细胞因子IL-10、TGF-β、IL-17水平变化与RSV毛细支气管炎发病的关系.方法:收集2010-09/2011-04在滨州医学院附属医院儿科住院的33例RSV毛细支气管炎患儿、28例做为阳性对照的非RSV感染性肺炎患儿(肺炎组)及26例正常对照组的健康体检儿外周血,采用流式细胞术(FCM)检测外周血CD4+ CD25+调节性T细胞、Th17细胞百分率,酶联免疫吸附(ELISA)法检测血浆IL-10、TGF-β、IL-17的水平.结果:RSV毛细支气管炎患儿外周血CD4+ CD25+调节性T细胞、IL-10、TGF-β水平显著低于肺炎患儿及健康体检儿(P<0.05),而Th17、IL-17水平则显著高于肺炎患儿与健康体检儿(P<0

  14. The $\\alpha-\\alpha$ fishbone potential revisited

    CERN Document Server

    Day, J P; Elhanafy, M; Smith, E; Woodhouse, R; Papp, Z

    2011-01-01

    The fishbone potential of composite particles simulates the Pauli effect by nonlocal terms. We determine the $\\alpha-\\alpha$ fishbone potential by simultaneously fitting to two-$\\alpha$ resonance energies, experimental phase shifts and three-$\\alpha$ binding energies. We found that essentially a simple gaussian can provide a good description of two-$\\alpha$ and three-$\\alpha$ experimental data without invoking three-body potentials.

  15. Localization of type IV collagen a 1 to a 6 chains in basement membrane during mouse molar germ development.

    Science.gov (United States)

    Nagai, N; Nakano, K; Sado, Y; Naito, I; Gunduz, M; Tsujigiwa, H; Nagatsuka, H; Ninomiya, Y; Siar, C H

    2001-10-01

    The dental basement membrane (BM) putatively mediates epithelial-mesenchymal interactions during tooth morphogenesis and cytodifferentiation. Type IV collagen alpha chains, a major network-forming protein of the dental BM, was studied and results disclosed distinct expression patterns at different stages of mouse molar germ development. At the dental placode and bud stage, the BM of the oral epithelium expressed alpha 1, alpha 2, alpha 5 and alpha 6 chains while the gubernaculum dentis, in addition to the above four chains, also expressed a 4 chain. An asymmetrical expression for alpha 4, alpha 5 and alpha 6 chains was observed at the bud stage. At the early bell stage, the BM associated with the inner enamel epithelium (IEE) of molar germ expressed alpha 1, alpha 2 and alpha 4 chains while the BM of the outer enamel epithelium (OEE) expressed only alpha 1 and a 2 chains. With the onset of dentinogenesis, the collagen a chain profile of the IEE BM gradually disappeared. Howeverfrom the early to late bell stage, the gubernaculum dentis consistently expressed alpha 1, alpha 2, alpha 5 and a 6 chains resembling fetal oral mucosa. These findings suggest that stage- and position-specific distribution of type IV collagen alpha subunits occur during molar germ development and that these changes are essential for molar morphogenesis and cytodifferentiation. PMID:11732842

  16. Alpha One Foundation

    Science.gov (United States)

    ... Tested Find Support Find Doctor What Is Alpha-1? Alpha-1 Antitrypsin Deficiency (Alpha-1) is a ... results for inhaled augmentation More News Our Number One Goal: Find a cure for Alpha-1. Website ...

  17. 维生素A和布地奈德对哮喘大鼠外周血T细胞亚群和调节性T细胞的影响%The effects of vitamin A and budesonide on serum T-lymphocyte subsets and CD4 + CD25 + regulatory T cells in rat asthma model

    Institute of Scientific and Technical Information of China (English)

    何金根; 潘家华; 楼皖玲; 刘辉

    2011-01-01

    目的:探讨维生素A(Vit A)和布地奈德对哮喘大鼠外周血T细胞亚群和CD4+ CD25+ 调节性T细胞(CD4+ CD25+regulatory T cell,CD4+ CD25+ Treg)的影响,为其在哮喘防治中的应用提供实验依据.方法:将42只SD大鼠用卵蛋白建立哮喘模型,随机分成布地奈德治疗组、Vit A治疗组和哮喘对照组,每组各14只,各组干预1周,于第4周和第5周取外周血50μl,流式细胞术检测T细胞亚群及Treg细胞变化.结果:激发后第4周,Vit A组CD3+T细胞、CD4+ CD25+ Treg细胞显著高于布地奈德组(P<0.05),CD3+ CD8+ T细胞均低于布地奈德组(P<0.05);布地奈德组CD4+ CD25+ Treg细胞显著低于哮喘组(P<0.01);激发后第5周,布地奈德组CD4+ CD25+ Treg细胞低于哮喘组(P<0.05).结论:雾化吸入Vit A可减轻哮喘大鼠炎症反应,这一作用可能与哮喘大鼠外周血CD3+ T细胞和CIM+ CD25+ Treg细胞升高、CD8+ T细胞降低有关.%Objective:To investigate the effects of vitamin A and budesonide on peripheral blood T-lymphocyte subsets and CD4 +CD25 + Treg cells in rat asthma model, which provide the experimental basis for vitamin A in the prevention and treatment of bronchial asthma. Methods :Forty-two adult female SD rats were divided into three groups, the budesonide group, vitamin A group and asthma group. There were 14 rats in each group. The peripheral blood was conducted to determinate T-lymphocyte subsets and CD4 + CD25 + Treg by flow cytometry. Results: After the 4th of stimulation, CD3 + T cell and CD4 + CD25 + Treg cells in vitamin A group were significantly higher than those in budesonide group. CD3 + CD8 + T cell in vitamin A group was significantly lower than that in asthma group ( P < 0.05 ). CD4 + CD25 + Treg cells of budesonide group was significantly lower than that in asthma group ( P < 0.01 ). After the 5th of stimulation, CD4 + CD25 + Treg cells in budesonide group was significantly lower than that in asthma group ( P < 0. 05 ).Conclusions

  18. Ascaris lumbricoides-induced suppression of total and specific IgE responses in atopic subjects is interleukin 10-independent and associated with an increase of CD25(+) cells.

    Science.gov (United States)

    Matera, Giovanni; Giancotti, Aida; Scalise, Sonia; Pulicari, Maria Concetta; Maselli, Rosario; Piizzi, Chiara; Pelaia, Girolamo; Tancrè, Valentina; Muto, Valentina; Doldo, Patrizia; Cosco, Vincenzo; Cosimo, Paola; Capicotto, Renata; Quirino, Angela; Scalzo, Rosaria; Liberto, Maria Carla; Parlato, Giuseppe; Focà, Alfredo

    2008-11-01

    Ascaris presence in humans has been associated with high levels of blood eosinophils and serum IgE. This study was designed to address the influence of Ascaris infection on allergic and inflammatory parameters of atopic subjects. A cross-sectional design was used, and atopic individuals to be assessed were divided into 3 groups including Ascaris-infected, anti-Ascaris IgG-positive (seropositive), and control subjects. All subjects enrolled had positive skin test reactivity to at least 1 perennial or seasonal allergen; however, levels of C-reactive protein, C3, and C4 were within normal range values. Eosinophil percentage was not significantly different among the groups studied. Total IgE and specific anti-Ascaris IgE levels in the seropositive group were significantly higher than concentrations found in both control and infected groups. Interleukin (IL)-4 release in Ascaris-infected patients was significantly increased versus seropositives, who were able to produce more IL-4 than controls. The levels of IL-10 were lower in the seropositives as well as infected subjects in comparison with controls. CD25(+) lymphocyte populations were significantly increased in the infected group versus the seropositives as well as the controls. Lung function tests of some selected seropositive subjects were significantly impaired. The same parameters of a representative infected patient were not different from controls. Our data on T helper type 2 cells (Th2) and regulatory T cells (Treg) features, as well as CD25(+) lymphocyte increase, suggest an Ascaris-induced mechanism leading to parasite survival. Moreover, the stable control of both T helper type 1 cells (Th1) and Th2 immunity cascades, paralleled by the absence of overwhelming inflammatory systemic reactions and lack of allergic syndromes, may result in a favorable host condition.

  19. CD4+CD25hiFOXP3+ cells in cord blood of neonates born from filaria infected mother are negatively associated with CD4+Tbet+ and CD4+RORγt+ T cells.

    Directory of Open Access Journals (Sweden)

    Ulysse Ateba-Ngoa

    Full Text Available BACKGROUND: Children who have been exposed in utero to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how in utero exposure to parasite antigens affects cellular immune responses. METHODOLOGY: Here, 30 pregnant women were examined for the presence of microfilaria of Loa loa and Mansonella perstans in peripheral blood. At delivery, cord blood mononuclear cells (CBMC were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3. RESULTS: No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells. However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively. CONCLUSION: Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check.

  20. 自身免疫性血小板减少性紫癜患者外周血中CD4+CD25+调节性T细胞、sFas和sFasL的表达及临床意义%Expression and Clinical Significance of CD4 + CD25 + Treg Cells, sFas and sFasL in Peripheral Blood of Patients with Autoimmune Thrombocytopenic Purpura

    Institute of Scientific and Technical Information of China (English)

    贾瑞萍; 赵雪芸

    2011-01-01

    本研究通过检测成人自身免疫性血小板减少性紫癜(AITP)外周血中CI4+CD25+调节性T细胞(Treg)、sFas和sFasL的表达,探讨它们在AITP发病机制中的作用及临床意义,为寻求AITP治疗的有效方法提供理论依据.采用流式细胞术分别检测30例AITP患者和18例正常对照者外周血CD4+T、Treg、CD4+ CD25-T细胞表达率及Treg/CD4+T比值;用酶联免疫吸附法(ELISA)检测AITP患者治疗前后及对照组外周血sFas、sFasL表达水平.结果表明,AITP组外周血中CD4+T细胞表达率低于对照组(p<0.05),Treg细胞表达率及Treg/CD4+T比值明显低于正常对照组(p<0.0l).AITP组患者治疗前外周血中sFas和sFasL水平明显高于治疗后和正常对照组(p<0.01),AITP组治疗后与正常对照组外周血sFas、sFasL水平差异无统计学意义(p>0.05).AITP患者治疗前Treg细胞表达率、Treg/CD4+T细胞比值与血小板计数呈正相关;AITP患者外周血中sFas和sFasL水平呈正相关;CD4+T细胞、CD4+CD25 -T细胞表达率,sFas、sFasL浓度与血小板计数无明显相关;Treg细胞表达率和sFas、sFasL浓度间没有明显相关性.结论:Treg在AITP的发病机制中发挥一定作用;Treg细胞水平与AITP病情的严重程度有关;sFas和sFasL水平异常参与了AITP的免疫病理过程.%This study was aimed to detect the expression of CD4 * CD25 * regulatory T cells (Treg) , sFas and sFasL in patients with autoimmune thrombocytopenic purpura ( AITP) , and to explore their roles in the pathogenesis of AITP and clinical significance, so as to provie a theoretical basis for effective treatment for AITP. The expressions of CD4 * T, Treg, CD4 * CD25" T, Treg /CD4 * T in peripheral blood of 30 the patients with AITP and 18 controls were detected by flow cytometry, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of sFas and sFasL in peripheral blood of controls and the patients with AITP before and after treatment. The

  1. Falling chains

    Science.gov (United States)

    Wong, Chun Wa; Yasui, Kosuke

    2006-06-01

    The one-dimensional fall of a folded chain with one end suspended from a rigid support and a chain falling from a resting heap on a table is studied. Because their Lagrangians contain no explicit time dependence, the falling chains are conservative systems. Their equations of motion are shown to contain a term that enforces energy conservation when masses are transferred between subchains. We show that Cayley's 1857 energy nonconserving solution for a chain falling from a resting heap is incorrect because it neglects the energy gained when a link leaves a subchain. The maximum chain tension measured by Calkin and March for the falling folded chain is given a simple if rough interpretation. Other aspects of the falling folded chain are briefly discussed.

  2. Unwrapping Chains

    CERN Document Server

    Cambou, A D; Hamm, E; Hanna, J A; Menon, N; Santangelo, C D; Walsh, L

    2012-01-01

    A loop of chain can move along its own tangents, maintaining a steady shape. An open-ended chain undergoing a nontrivial motion must change its shape. One consequence is that chains pulled around objects will fail to follow the contours of the objects, unwrapping themselves instead. This short note accompanies a fluid dynamics video submission (83068) to the APS DFD Gallery of Fluid Motion 2012.

  3. Falling chains

    CERN Document Server

    Wong, C W; Wong, Chun Wa; Yasui, Kosuke

    2006-01-01

    The one-dimensional falling motion of a bungee chain suspended from a rigid support and of a chain falling from a resting heap on a table is studied. Their Lagrangians are found to contain no explicit time dependence. As a result, these falling chains are conservative systems. Each of their Lagrange's equations of motion is shown to contain a term that enforces energy conservation when masses are transferred between subchains. We show in particular that Cayley's 1857 energy nonconserving solution for a chain falling from a resting heap is incorrect because it neglects the energy gained when the transferred link is emitted by the emitting subchain. The maximum chain tension measured by Calkin and March for the falling bungee chain is given a simple if rough interpretation. In the simplified one-dimensional treatment, the kinetic energy of the center of mass of the falling bungee chain is found to be converted by the chain tension at the rigid support into the internal kinetic energy of the chain. However, as t...

  4. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection

    International Nuclear Information System (INIS)

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-γ by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4+CD25highFoxp3+ regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  5. Main Regulatory Factors for Differentiation,Development and Function of Naturally Occurred CD4+CD25+Regulatory T Cells——Review%天然调节性T细胞的调节因素研究进展

    Institute of Scientific and Technical Information of China (English)

    吴敏; 谢彦晖

    2008-01-01

    天然CD4+CD25+调节T细胞来源于胸腺,通过直接接触机制抑制效应细胞的增殖,调节自身免疫和移植免疫.本文主要综述了影响天然调节T细胞分化、发育和功能的主要因素和可能机制.Foxp3是Treg的标志,检测其表达可以作为判定Treg的方法.IL-2主要通过IL-2Rα及STAT5途径促进Treg的增殖活化.膜型和分泌型TGF-β具有不同功能,膜型TGF-β1可能主要介导Treg的抑制功能,而分泌型TGF-β可能主要促进Treg的增殖.树突状细胞由于作用途径不同,对Treg既有正调节,也有负调节.CTLA-4途径可能通过作用于Treg自身、DC或效应细胞直接或间接地调节Treg的功能.

  6. Freeze and Thaw of CD4+CD25+Foxp3+ Regulatory T Cells Results in Loss of CD62L Expression and a Reduced Capacity to Protect against Graft-versus-Host Disease.

    Directory of Open Access Journals (Sweden)

    Mareike Florek

    Full Text Available The adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs in murine models of allogeneic hematopoietic cell transplantation (HCT has been shown to protect recipient mice from lethal acute graft-versus-host disease (GVHD and this approach is being actively investigated in human clinical trials. Here, we examined the effects of cryopreservation on Tregs. We found that freeze and thaw of murine and human Tregs is associated with reduced expression of L-selectin (CD62L, which was previously established to be an important factor that contributes to the in vivo protective effects of Tregs. Frozen and thawed murine Tregs showed a reduced capacity to bind to the CD62L binding partner MADCAM1 in vitro as well as an impaired homing to secondary lymphoid organs in vivo. Upon adoptive transfer frozen and thawed Tregs failed to protect against lethal GVHD compared with fresh Tregs in a murine model of allogeneic HCT across major histocompatibility barriers. In summary, the direct administration of adoptively transferred frozen and thawed Tregs adversely affects their immunosuppressive potential which is an important factor to consider in the clinical implementation of Treg immunotherapies.

  7. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, De-Hua [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Dou, Li-Ping [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China); Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Shi, Bing-Yi, E-mail: shibingyi@medmail.com.cn [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)

    2010-05-14

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  8. NY-ESO-1-specific circulating CD4+ T cells in ovarian cancer patients are prevalently T(H)1 type cells undetectable in the CD25+ FOXP3+ Treg compartment.

    Science.gov (United States)

    Redjimi, Nassima; Duperrier-Amouriaux, Karine; Raimbaud, Isabelle; Luescher, Immanuel; Dojcinovic, Danijel; Classe, Jean-Marc; Berton-Rigaud, Dominique; Frenel, Jean-Sébastien; Bourbouloux, Emmanuelle; Valmori, Danila; Ayyoub, Maha

    2011-01-01

    Spontaneous CD4(+) T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4(+) T cells in EOC patients with spontaneous immune responses to the antigen are prevalently T(H)1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer(+) cells ex vivo, at an average frequency of 1:25,000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer(+) cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25(+)FOXP3(+)Treg. Thus, spontaneous CD4(+) T-cell responses to ESO in cancer patients are prevalently of T(H)1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines.

  9. Significance of serum CD25/serum ferritin in the diagnosis of lymphoma-associated hemophagocytic syndrome%可溶性白细胞介素2受体/血清铁蛋白对诊断淋巴瘤相关性噬血细胞综合征的意义

    Institute of Scientific and Technical Information of China (English)

    吴道香; 王昭; 王晓琳; 林榕榕; 刘暖; 张嘉

    2012-01-01

    目的 探讨可溶性白细胞介素2受体( sCD25)/血清铁蛋白在诊断淋巴瘤相关性噬血细胞综合征( LAHS)中的意义,为进一步提高LAHS诊断率,及时诊断和治疗LAHS提供临床依据.方法 收集2008年10月至2011年6月首都医科大学附属北京友谊医院经诊的确诊噬血细胞综合征患者70例,包括31例LAHS和39例非LAHS.收集所有患者血清,采用酶联免疫吸附法(ELISA)检测其sCD25水平,并于当日检测血清铁蛋白水平,然后计算sCD25和血清铁蛋白的比值,并比较LAHS和非LAHS之间血清sCD25、血清铁蛋白以及sCD25/血清铁蛋白有无差异.结果 LAHS和非LAHS患者sCD25质量浓度分别为(15760.52±7851.74)、(12727.41±11285.28) pg/ml(t=-1.78,P=0.075,血清铁蛋白中位质量浓度分别为1750.00、2947.00 ng/ml(Z=-1.490,P=0.136),sCD25/血清铁蛋白中位比值分别为8.57×10-3、2.84×10-3,差异具有统计学意义(Z=-2.106,P=0.035).结论 sCD25/血清铁蛋白在LAHS中明显升高,对诊断LAHS具有重要的提示意义,有可能成为诊断LAHS的重要指标.%Objective To investigate the significance of serum CD25 / serum ferritin in the diagnosis of lymphoma-associated hemophagocytic syndrome (LAHS),so as to provide the clinical basis for improving its recognition and giving effective therapy. Methods The serums were collected from 70 patients with hemophagocytic syndrom in Beijing Friendship Hospital, Capital Medical University during the period from October 2008 to June 2011, including 31 LAHS cases and 39 other disease-associated HPS cases. The serum CD25 level in HPS patients was measured with enzyme-linked immunosorbent assay (ELISA), and the serum ferritin was measured on the same day. Then the serum CD25/ferritin ratio was calculated and the differences of the serum CD25, serum ferritin and serum CD25/ferritin ratio between two groups were compared. Results The variance of serum CD25 [(15760.52±7851.74) pg/ml vs (12727.41±11285.28) pg/ml,t=-1.78,P

  10. Comparison of transcript levels and mRNA half-lives for the subunits of the branched-chain {alpha}-keto acid dehydrogenase (BCKD) complex in two human cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Bowers, B.A.; Danner, D.J. [Emory Univ., Atlanta, GA (United States)

    1994-09-01

    BCKD is a mitochondrial multienzyme complex that catalyzes the committed step in catabolism of the keto acid derivatives of leucine, isoleucine and valine. Three subunits, El{alpha}, E1{beta} and E2 are specific to the complex. The subunits are nuclearly encoded from genes located on separate chromosomes, and it is not yet understood how gene expression of the components is regulated to maintain proper stoichiometry of the complex. The focus of the present study is to establish mRNA half-lives for the BCKD subunits in two human cell lines and to examine whether expression of transcripts for the subunits is similar in different cell types. HepG2 cells, a hepatocarcinoma cell line, and DG75 cells, a Burkitt`s lymphoma cell line, express comparable levels of BCKD complex based on total enzyme activity. Half-lives of the mRNAs for each subunit have been determined in HepG2 cells and are presently being defined in DG75 cells. mRNA half-lives were calculated by quantifying message levels over a 24 hour period following an actinomycin D block. Transcripts for the BCKD subunits are relatively stable in HepG2 cells with mRNA half-lives for the E1{alpha} of 11 hours, E1{beta}, 24 hours and E2, 22 hours. Steady-state message levels have been analyzed in both cell lines by RNase protection and quantified as a percentage of total RNA. mRNA levels for all three subunits are higher in DG75 cells than in HepG2 cells (E1{alpha}, 4-fold; E1{beta}, 1.9-fold; E2, 1.8-fold). Preliminary data indicates that the half-life of the E1{alpha} transcript in DG75 cells is approximately 29 hours, and it is possible that differences in steady-state levels of the mRNAs are achieved through different half-lives of the transcripts. The relationship between transcript levels and protein levels for the three subunits is being examined in both cell types.

  11. Association of PD-1 expression on CD4~+CD25~(nt/hi)CD127~(lo) regulatory T cells with disease progression in HIV-1 infected patients%HIV-1感染者CD4~+CD25~(nt/hi)CD127~(lo)调节性T细胞PD-1表达水平与疾病进展的关系

    Institute of Scientific and Technical Information of China (English)

    曹清华; 薛以乐; 王盈

    2009-01-01

    目的:阐明HIV-1感染者外周血中具有CD4~+CD25~(nt/hi)CD127~(lo)特征的调节性T细胞(Treg)表面PD-1的表达水平与疾病进展的关系.方法:选取108名未经治疗的不同进展期的HIV-1感染者和27名健康人对照, 采集静脉血, 用Ficoll-Hypaque密度梯度离心法分离获得PBMC, 加入PerCP-CD4抗体、 FITC-CD25抗体、 PE-CD127抗体和APC-PD-1抗体, 经细胞表面四色染色、流式细胞术(FCM)分析Treg表面PD-1的表达;另将50 L全血加入Trucount绝对计数管, 采用Multitest CD3/CD8/CD45/CD4试剂盒检测CD4+T细胞绝对数;分离静脉血血浆, NucliSens EasyQ测定血浆HIV-1病毒载量;实验数据采用SPSS14.0 统计学软件分析处理.结果:HIV-1感染者Treg表面PD-1表达水平显著高于健康人(5.33%±2.24% vs 1.72%±0.65%, P<0.01);AIDS期(7.87%±2.23%)明显高于进展期(5.21%±1.72%, P<0.05)和新近感染者(3.22%±1.01%, P<0.05);HIV-1感染者Treg表面PD-1表达水平与血浆中的HIV-1病毒载量和CD4~+T细胞绝对数密切相关.结论:首次证实HIV-1感染者外周血中Treg表面PD-1表达增加, 且表达水平与病程进展相关.该结果为进一步揭示HIV-1感染中Treg的效应机制、探索新的免疫治疗方案提供了理论及实验依据.%AIM: To investigate whether Programmed death-1 (PD-1) expression on peripheral CD4~+CD25~(nt/hi)CD127~(lo) regulatory T cells (Treg) was associated with disease progression in HIV-1-infected patients. METHODS: Peripheral blood from 108 HIV-1-infected patients in distinct disease progression statuses and 27 healthy individuals were collected in the present investigation. PBMCs were isolated by centrifugation on Ficoll-Hypaque, followed by staining with anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE and anti-PD-1-APC. PD-1 expression on Treg was analyzed by four-color staining flow cytometry. CD4~+T cell absolute counts were determined using Multitest CD3/CD4/CD8/CD45 kit and plasma viral loads were detected on Nucli

  12. Role of mitochondrial transamination in branched chain amino acid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hutson, S.M.; Fenstermacher, D.; Mahar, C.

    1988-03-15

    Oxidative decarboxylation and transamination of 1-/sup 14/C-branched chain amino and alpha-keto acids were examined in mitochondria isolated from rat heart. Transamination was inhibited by aminooxyacetate, but not by L-cycloserine. At equimolar concentrations of alpha-ketoiso(1-/sup 14/C)valerate (KIV) and isoleucine, transamination was increased by disrupting the mitochondria with detergent which suggests transport may be one factor affecting the rate of transamination. Next, the subcellular distribution of the aminotransferase(s) was determined. Branched chain aminotransferase activity was measured using two concentrations of isoleucine as amino donor and (1-/sup 14/C)KIV as amino acceptor. The data show that branched chain aminotransferase activity is located exclusively in the mitochondria in rat heart. Metabolism of extramitochondrial branched chain alpha-keto acids was examined using 20 microM (1-/sup 14/C)KIV and alpha-ketoiso(1-/sup 14/C)caproate (KIC). There was rapid uptake and oxidation of labeled branched chain alpha-keto acid, and, regardless of the experimental condition, greater than 90% of the labeled keto acid substrate was metabolized during the 20-min incubation. When a branched chain amino acid (200 microM) or glutamate (5 mM) was present, 30-40% of the labeled keto acid was transaminated while the remainder was oxidized. Provision of an alternate amino acceptor in the form of alpha-keto-glutarate (0.5 mM) decreased transamination of the labeled KIV or KIC and increased oxidation. Metabolism of intramitochondrially generated branched chain alpha-keto acids was studied using (1-/sup 14/C)leucine and (1-/sup 14/C)valine. Essentially all of the labeled branched chain alpha-keto acid produced by transamination of (1-/sup 14/C)leucine or (1-/sup 14/C)valine with a low concentration of unlabeled branched chain alpha-keto acid (20 microM) was oxidized.

  13. Ab initio alpha-alpha scattering

    CERN Document Server

    Elhatisari, Serdar; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-01-01

    Processes involving alpha particles and alpha-like nuclei comprise a major part of stellar nucleosynthesis and hypothesized mechanisms for thermonuclear supernovae. In an effort towards understanding alpha processes from first principles, we describe in this letter the first ab initio calculation of alpha-alpha scattering. We use lattice effective field theory to describe the low-energy interactions of nucleons and apply a technique called the adiabatic projection method to reduce the eight-body system to an effective two-cluster system. We find good agreement between lattice results and experimental phase shifts for S-wave and D-wave scattering. The computational scaling with particle number suggests that alpha processes involving heavier nuclei are also within reach in the near future.

  14. Amino acid substitutions of conserved residues in the carboxyl-terminal domain of the [alpha]I(X) chain of type X collagen occur in two unrelated families with metaphyseal chondrodysplasia type Schmid

    Energy Technology Data Exchange (ETDEWEB)

    Wallis, G.A.; Rash, B.; Sweetman, W.A.; Thomas, J.T.; Grant, M.E.; Boot-Handford, R.P. (Univ. of Manchester (United Kingdom)); Super, M. (Royal Manchester Children' s Hospital, Manchester (United Kingdom)); Evans, G. (Robert Jones Orthopaedic Hospital, Oswestry (United Kingdom))

    1994-02-01

    Type X collagen is a homotrimeric, short-chain, nonfibrillar extracellular-matrix component that is specifically and transiently synthesized by hypertrophic chondrocytes at the site of endochondral ossification. The precise function of type X collagen is not known, but its specific pattern of expression suggests that mutations within the encoding gene (COL10A1) that alter the structure or synthesis of the protein may cause heritable forms of chondrodysplasia. The authors used the PCR and the SSCP techniques to analyze the coding and upstream promoter regions of the COL10A1 gene in a number of individuals with forms of chondrodysplasia. Using this approach, they identified two individuals with metaphyseal chondrodysplasia type Schmid (MCDS) with SSCP changes in the region of the gene encoding the carboxyl-terminal domain. Sequence analysis demonstrated that the individuals were heterozygous for two unique single-base-pair transitions that led to the substitution of the highly conserved amino acid residue tyrosine at position 598 by aspartic acid in one person and of leucine at position 614 by proline in the other. The substitution at residue 598 segregated with the phenotype in a family of eight (five affected and three unaffected) related persons. The substitutions at residue 614 occurred in a sporadically affected individual but not in her unaffected mother and brother. Additional members of this family were not available for further study. These results suggest that certain amino acid substitutions within the carboxyl-terminal domain of the chains of the type X collagen molecule cause MCDS. These amino acid substitutions are likely to alter either chain recognition or assembly of the type X collagen molecule, thereby depleting the amount of normal type X collagen deposited in the extracellular matrix, with consequent aberrations in bone growth and development. 36 refs., 5 figs.

  15. 前列腺癌患者手术前后外周血调节性T细胞和FOXP3mRNA的表达及临床意义%Levels of CD4+CD25+Regulatory T Cells & Expression of FOXP3 mRNA after Operation in Peripheral Blood from Patients with Prostate Cancer and its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    章更生

    2011-01-01

    目的 探讨前列腺癌(Pca)患者手术前后外周血CD4+CD25+调节性T细胞(Tregs)及其特异标志物FOXP3mRNA的表达比例的变化及临床意义.方法 应用流式细胞术检测50例前列腺癌及50例正常对照组外周血单个核细胞(PBMC)中Tregs占CD4+T细胞的比例,应用RT-PCR技术检测人外周血PBMC FOXP3 mRNA的表达.结果 随着Gleason分级升高,CD4+CD25+Tregs/CD4+T比值和FOXP3 mRNA表达量均有升高趋势;Pca患者术前CD4+CD25+ Treg细胞占CD4+T细胞的比例和FOXP3 mRNA表达水平高于正常对照组(均P<0.05),术后水平与正常对照组差异无统计学意义;Pca组Tregs表达率与FOXP3 mRNA呈正相关(r=0.623,P<0.01).结论 Tregs及其特异标志物FOXP3具有维持自身免疫稳定和抑制肿瘤免疫作用,可能参与前列腺癌的发生.%Objective To explore the rate change of CD4+ CD25+ regulatory T cells and expression of F0XP3 mRNA after operation in peripheral blood from patients with prostate cancer and its clinical significance. Methods Flow cytometry was used to analyze the proportion of CD4+CD25+ regulatory T cells/CD4T cells in peripheral blood mononuclear cells (PBMC) among 50 patients with prostate cancer and 50 healthy controls. The expression of FOXP3 mRNA in PBMC was detected by RT-PCR. Results The value of CD4+CU25+Tregs/CD4+ T cells and expression of FOXP3 mRNA were increased with Gleason pathological parameters increased. And the value of CD4+CD25+ regulatory T cells/CD4+T cells and expression of FOXP3 mRNA in PBMC from patients with prostate cancer before operation were significantly higher than that of the healthy controls. But there were no statistical significance between patients with prostate cancer after operation and healthy controls. Correlative analysis showed that there was a positive correlation between the CD4+CD25+ regulatory T cells and the expression of F0XP3 mRNA in PBMC of the patients with prostate cancer (r=0.623,p<0.01). Conclusion CD4+CD25

  16. Two Cases of Heavy Chain MGUS.

    Science.gov (United States)

    Van Keer, Jan; Meijers, Björn; Delforge, Michel; Verhoef, Gregor; Poesen, Koen

    2016-01-01

    Heavy chain diseases are rare variants of B-cell lymphomas that produce one of three classes of immunoglobulin heavy chains, without corresponding light chains. We describe two patients with asymptomatic heavy chain monoclonal gammopathy. The first patient is a 51-year-old woman with alpha paraprotein on serum immunofixation. The second case is a 46-year-old woman with gamma paraprotein on urine immunofixation. Neither patient had corresponding monoclonal light chains. Workup for multiple myeloma and lymphoma was negative in both patients. These two cases illustrate that heavy chain monoclonal gammopathy can exist in the absence of clinically apparent malignancy. Only a few reports of "heavy chain MGUS" have been described before. In the absence of specialized guidelines, we suggest a similar follow-up as for MGUS, while taking into account the higher probability of progression to lymphoma than to myeloma. PMID:27213064

  17. Two Cases of Heavy Chain MGUS

    Directory of Open Access Journals (Sweden)

    Jan Van Keer

    2016-01-01

    Full Text Available Heavy chain diseases are rare variants of B-cell lymphomas that produce one of three classes of immunoglobulin heavy chains, without corresponding light chains. We describe two patients with asymptomatic heavy chain monoclonal gammopathy. The first patient is a 51-year-old woman with alpha paraprotein on serum immunofixation. The second case is a 46-year-old woman with gamma paraprotein on urine immunofixation. Neither patient had corresponding monoclonal light chains. Workup for multiple myeloma and lymphoma was negative in both patients. These two cases illustrate that heavy chain monoclonal gammopathy can exist in the absence of clinically apparent malignancy. Only a few reports of “heavy chain MGUS” have been described before. In the absence of specialized guidelines, we suggest a similar follow-up as for MGUS, while taking into account the higher probability of progression to lymphoma than to myeloma.

  18. Ab initio alpha-alpha scattering

    Science.gov (United States)

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A.; Luu, Thomas; Meißner, Ulf-G.

    2015-12-01

    Processes such as the scattering of alpha particles (4He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei—nuclei with even and equal numbers of protons and neutrons—is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the ‘adiabatic projection method’ to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  19. Ab initio alpha-alpha scattering.

    Science.gov (United States)

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-12-01

    Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei--nuclei with even and equal numbers of protons and neutrons--is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the 'adiabatic projection method' to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  20. beta-Hexosaminidase isozymes from cells cotransfected with alpha and beta cDNA constructs: analysis of the alpha-subunit missense mutation associated with the adult form of Tay-Sachs disease.

    OpenAIRE

    Brown, C. A.; Mahuran, D. J.

    1993-01-01

    In vitro mutagenesis and transient expression in COS cells has been used to associate a missense mutation with a clinical or biochemical phenotype. Mutations affecting the alpha-subunit of beta-hexosaminidase A (alpha beta) (E.C.3.2.1.52) result in Tay-Sachs disease. Because hexosaminidase A is heterodimeric, analysis of alpha-chain mutations is not straightforward. We examine three approaches utilizing previously identified mutations affecting alpha-chain folding. These involve transfection ...

  1. Chain Gang

    Science.gov (United States)

    2006-01-01

    6 August 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a chain of clustered and battered craters. These were formed by secondary impact. That is, somewhere to the south (beyond the bottom of this image), a large impact crater formed. When this occurred, material ejected from the crater was thrown tens to hundreds of kilometers away. This material then impacted the martian surface, forming clusters and chains of smaller craters. Location near: 15.8oN, 35.6oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Northern Spring

  2. HIV-1 p17 matrix protein interacts with heparan sulfate side chain of CD44v3, syndecan-2, and syndecan-4 proteoglycans expressed on human activated CD4+ T cells affecting tumor necrosis factor alpha and interleukin 2 production.

    Science.gov (United States)

    De Francesco, Maria A; Baronio, Manuela; Poiesi, Claudio

    2011-06-01

    HIV-1 p17 contains C- and N-terminal sequences with positively charged residues and a consensus cluster for heparin binding. We have previously demonstrated by affinity chromatography that HIV-1 p17 binds strongly to heparin-agarose at physiological pH and to human activated CD4(+) T cells. In this study we demonstrated that the viral protein binds to heparan sulfate side chains of syndecan-2, syndecan-4, and CD44v3 purified from HeLa cells and that these heparan sulfate proteoglycans (HSPGs) co-localize with HIV-1 p17 on activated human CD4(+) T cells by confocal fluorescence analysis. Moreover, we observed a stimulatory or inhibitory activity when CD4(+) T cells were activated with mitogens together with nanomolar or micromolar concentrations of the matrix protein.

  3. Effect of Low Electric Fields on Alpha Scintillation Light Yield in Liquid Argon

    CERN Document Server

    Agnes, P; Alexander, T; Alton, A K; Asner, D M; Back, H O; Baldin, B; Biery, K; Bocci, V; Bonfini, G; Bonivento, W; Bossa, M; Bottino, B; Brigatti, A; Brodsky, J; Budano, F; Bussino, S; Cadeddu, M; Cadoni, M; Calaprice, F; Canci, N; Candela, A; Caravati, M; Cariello, M; Carlini, M; Catalanotti, S; Cavalcante, P; Chepurnov, A; Cicalò, C; Cocco, A G; Covone, G; D'Angelo, D; D'Incecco, M; Davini, S; De Cecco, S; De Deo, M; De Vincenzi, M; Derbin, A; Devoto, A; Di Eusanio, F; Di Pietro, G; Dionisi, C; Edkins, E; Empl, A; Fan, A; Fiorillo, G; Fomenko, K; Forster, G; Franco, D; Gabriele, F; Galbiati, C; Giagu, S; Giganti, C; Giovanetti, G K; Goretti, A M; Granato, F; Gromov, M; Guan, M; Guardincerri, Y; Hackett, B R; Herner, K; Hughes, D; Humble, P; Hungerford, E V; Ianni, A; James, I; Johnson, T N; Jollet, C; Keeter, K; Kendziora, C L; Koh, G; Korablev, D; Korga, G; Kubankin, A; Li, X; Lissia, M; Loer, B; Lombardi, P; Longo, G; Ma, Y; Machulin, I N; Mandarano, A; Mari, S M; Maricic, J; Marini, L; Martoff, C J; Meregaglia, A; Meyers, P D; Milincic, R; Miller, J D; Montanari, D; Monte, A; Mount, B J; Muratova, V N; Musico, P; Napolitano, J; Agasson, A Navrer; Odrowski, S; Oleinik, A; Orsini, M; Ortica, F; Pagani, L; Pallavicini, M; Pantic, E; Parmeggiano, S; Pelczar, K; Pelliccia, N; Pocar, A; Pordes, S; Pugachev, D A; Qian, H; Randle, K; Ranucci, G; Razeti, M; Razeto, A; Reinhold, B; Renshaw, A L; Rescigno, M; Riffard, Q; Romani, A; Rossi, B; Rossi, N; Rountree, D; Sablone, D; Saggese, P; Sands, W; Savarese, C; Schlitzer, B; Segreto, E; Semenov, D A; Shields, E; Singh, P N; Skorokhvatov, M D; Smirnov, O; Sotnikov, A; Stanford, C; Suvorov, Y; Tartaglia, R; Tatarowicz, J; Testera, G; Tonazzo, A; Trinchese, P; Unzhakov, E V; Verducci, M; Vishneva, A; Vogelaar, B; Wada, M; Walker, S; Wang, H; Wang, Y; Watson, A W; Westerdale, S; Wilhelmi, J; Wojcik, M M; Xiang, X; Xiao, X; Xu, J; Yang, C; Zhong, W; Zhu, C; Zuzel, G

    2016-01-01

    Measurements were made of scintillation light yield of alpha particles from the $^{222}$Rn decay chain within the DarkSide-50 liquid argon time projection chamber. The light yield was found to increase as the applied electric field increased, with alphas in a 200 V/cm electric field exhibiting a $\\sim$2% increase in light yield compared to alphas in no field.

  4. Hemeoxygenase-1 expression effect on the up-regulation of peripheral blood CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells in asthma patients%血红素加氧酶1在间充质干细胞上调哮喘患者外周血调节性T细胞中的作用

    Institute of Scientific and Technical Information of China (English)

    温冰; 颛孙永勋; 颜富德; 陈瑞; 张蔚; 冯素玲; 李建国

    2011-01-01

    BACKGROUND: Up-regulating CD4+CD25+CD127low/- regulatory T cells is a new target in the treatment of asthma. Human bone marrow mesenchymal stem cells (MSCs) can up-regulate CD4+CD25+CD127low/- regulatory T cells in vitro, while the mechanism is not clear.OBJECTIVE: To study the effect of hemeoxygenase -1 (HO-1) expression in the up-regulation of peripheral blood CD4+CD25+CD127low/- regulatory T cells mediated by MSCs in asthma patients.METHODS: Real-time PCR was used to examine the expression of HO-1 mRNA in MSCs pretreated with 0, 15, 30, 45,60 μmol/L Hemin (the revulsive of HO-1) and 0, 5, 10, 15, 20 μmol/L ZnPP (the inhibitor of HO-1) respectively. Peripheral blood mononuclear cells (PBMCs), which were isolated from 10 cases of asthma patients with acute episode and 10 cases of healthy controls using Ficoll density gradient centrifugation, were incubated with MSCs pretreated with Hemin, ZnPP and mock respectively.RESULTS AND CONCLUSION: The expression of HO-1 in MSCs can be induced and inhibited in vitro. The higher concentration of Hemin added to MSCs, the higher expression of HO-1 mRNA was tested (P < 0.05). With the increasing concentration of ZnPP added to MSCs, the expression of HO-1 mRNA was becoming lower (P < 0.05). The proportion of CD4 +CD25+CD127low/-regulatory T cells in CD4+ T cells could be up-regulated by MSCs (P < 0.01) and also by MSCs with induction of HO-1 expression (P < 0.01). While MSCs with inhibition of HO-1 expression could down-regulate the proportion of CD4 +CD25+CD127low/-regulatory T cells in CD4 + T cells (P < 0.01). The expression of HO-1 partially contributed to the up-regulation of CD4+CD25+CD127low/- regulatory T cells mediated by MSCs in asthma patients.%背景:上调CD4+CD25+CD127low/-调节性T 细胞是目前治疗哮喘的新靶点.骨髓间充质干细胞在体外可上调正常人外周血的调节性T 细胞,但机制尚未明确.目的:观察血红素加氧酶1 对间充质干细胞

  5. Faddeev calculation of 3 alpha and alpha alpha Lambda systems using alpha alpha resonating-group method kernel

    CERN Document Server

    Fujiwara, Y; Kohno, M; Suzuki, Y; Baye, D; Sparenberg, J M

    2004-01-01

    We carry out Faddeev calculations of three-alpha (3 alpha) and two-alpha plus Lambda (alpha alpha Lambda) systems, using two-cluster resonating-group method kernels. The input includes an effective two-nucleon force for the alpha alpha resonating-group method and a new effective Lambda N force for the Lambda alpha interaction. The latter force is a simple two-range Gaussian potential for each spin-singlet and triplet state, generated from the phase-shift behavior of the quark-model hyperon-nucleon interaction, fss2, by using an inversion method based on supersymmetric quantum mechanics. Owing to the exact treatment of the Pauli-forbidden states between the clusters, the present three-cluster Faddeev formalism can describe the mutually related, alpha alpha, 3 alpha and alpha alpha Lambda systems, in terms of a unique set of the baryon-baryon interactions. For the three-range Minnesota force which describes the alpha alpha phase shifts quite accurately, the ground-state and excitation energies of 9Be Lambda are...

  6. Molecular design of the C alpha beta interface favors specific pairing of introduced TCR alpha beta in human T cells

    NARCIS (Netherlands)

    Voss, Ralf-Holger; Willemsen, Ralph A.; Kuball, Juergen; Grabowski, Margarete; Engel, Renate; Intan, Ratna S.; Guillaume, Philippe; Romero, Pedro; Huber, Christoph; Theobald, Matthias

    2008-01-01

    A promising approach to adoptive transfer therapy of tumors is to reprogram autologous T lymphocytes by TCR gene transfer of defined Ag specificity. An obstacle, however, is the undesired pairing of introduced TCR alpha- and TCR beta-chains with the endogenous TCR chains. These events vary depending

  7. Chain Teleportation

    OpenAIRE

    Lee, Chien-er

    2004-01-01

    By means of the idea of measurements on the crossed space-time nonlocal observables, we extend the mechanism for the two-way quantum teleportation to the chain teleportation among N spatially separated spin-1/2 systems. Since in the process only the local interactions are used, the microcausality is automatically satisfied.

  8. An experimental study of the relationship between CD4+CD25+T regulatory cells and the Th1/Th2 imbalance in asthmatic mice%哮喘小鼠调节性T细胞与Th1/Th2因子失衡关系的实验研究

    Institute of Scientific and Technical Information of China (English)

    綦梅伶; 路明; 武怡; 吴铭

    2011-01-01

    Objective To investigate the effect of the variations of CD4 +CD25 + T regulatory cell counts in the peripheral blood in mouse model of asthma on the expressions of serum Th1/Th2 - related cytokines, IFN - γ/ and IL - 4,and to explore their roles in the pathogenesis of bronchial asthma. Methods Twenty healthy female BALB/c mice were randomized into two groups ( n = 10 each ). The mice in the model group were subjected to intraperitoneal injection of OVA/AIC OH )3 on days 0, 7 and 14 respectively, followed by challenge with inhalation of nebulized OVA daily from days 21 to 26. The control group underwent treatment with normal saline instead of OVA for intraperitoneal injection during primary sensitization and aerosol inhalation during secondary induction. The animals were sacrificed on day 27. The histopathological changes of the murine pulmonary tissues were observed by microscopy. The variations in CD4+ CD25 + T+ regulatory cell counts in the blood and expression levels of the cytokines 1L -4 and IFN - γ/ in the serum were determined by flow cytometry and ELISA, respectively. Results The counts of CD4+CD25 +T regulatory cells in the peripheral blood.their proportion in CD4 + T cells and the serum IFN - γ level were significantly lower ( P <0. 01 ) and serum 1L -4 level was significantly higher ( P <0. 01 ) in the model group than those in the control group. Conclusion Asthmatic mice show an evident Th1/Th2 imbalance, with the hyperfunction of the Th2 , and its ruechanism is related to the decreased inhibition of CD4 + CD25 + T regulatory cells.%目的 研究哮喘小鼠外周血CD4+CD25+Treg细胞数量改变与血清Th1/Th2相关细胞因子IFN-γ和IL-4水平的关系,探讨其在支气管哮喘发病中的作用.方法 健康雌性BALB/c小鼠20只,随机分为2组(每组10只):①模型组于第0、7、14天予OVA/Al(OH)3腹腔注射,第21~26天每天以OVA雾化吸入激发.②对照组则以生理盐

  9. Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues.

    Science.gov (United States)

    Eason, M G; Liggett, S B

    1993-07-01

    At present, molecular cloning and pharmacological studies have delineated three human alpha 2-adrenergic receptor (alpha 2AR) subtypes, alpha 2C10, alpha 2C4, and alpha 2C2. Assignment of the alpha 2AR subtypes to specific functions has been limited by an unclear definition of tissue alpha 2AR expression outside of the central nervous system. It has been suggested that alpha 2C4 expression is confined to the brain, that alpha 2C2 expression is only in the liver and kidney, and that there is nearly ubiquitous expression of alpha 2C10. However, this is based on studies of a limited number of rat tissues or on studies using non-species-specific approaches. Therefore, to define alpha 2C10, alpha 2C4, and alpha 2C2 tissue expression, we used reverse transcription of total RNA isolated from 20 human tissues, followed by amplification of alpha 2AR cDNA using the polymerase chain reaction. This technique provided two advantages: high sensitivity and, with the use of subtype-specific oligonucleotide primers and probes, differentiation between the alpha 2AR subtypes. The tissues studied were aorta, vena cava, heart (epicardium and endocardium), lung, skeletal muscle, liver, pancreas (head and tail), fat (perinephric and subcutaneous), kidney (cortex and medulla), prostate, stomach, ileum, jejunum, colon, adrenal gland, and spleen. We found that the majority of these tissues expressed alpha 2C10, with the exceptions being the head of the pancreas, subcutaneous fat, colon, and spleen. In marked distinction to other studies, however, we found a prolific expression of the alpha 2C4 and alpha 2C2 subtypes. Expression of alpha 2C4 was found in all tissues with the exception of liver, fat, stomach, and colon, and a virtually ubiquitous expression of alpha 2C2 was found, with the exception of epicardium. Of all tissues studied, only colon and subcutaneous fat expressed a single alpha 2AR subtype, which was alpha 2C2. Thus, the alpha 2AR subtypes do not have a confined expression but

  10. Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues.

    Science.gov (United States)

    Eason, M G; Liggett, S B

    1993-07-01

    At present, molecular cloning and pharmacological studies have delineated three human alpha 2-adrenergic receptor (alpha 2AR) subtypes, alpha 2C10, alpha 2C4, and alpha 2C2. Assignment of the alpha 2AR subtypes to specific functions has been limited by an unclear definition of tissue alpha 2AR expression outside of the central nervous system. It has been suggested that alpha 2C4 expression is confined to the brain, that alpha 2C2 expression is only in the liver and kidney, and that there is nearly ubiquitous expression of alpha 2C10. However, this is based on studies of a limited number of rat tissues or on studies using non-species-specific approaches. Therefore, to define alpha 2C10, alpha 2C4, and alpha 2C2 tissue expression, we used reverse transcription of total RNA isolated from 20 human tissues, followed by amplification of alpha 2AR cDNA using the polymerase chain reaction. This technique provided two advantages: high sensitivity and, with the use of subtype-specific oligonucleotide primers and probes, differentiation between the alpha 2AR subtypes. The tissues studied were aorta, vena cava, heart (epicardium and endocardium), lung, skeletal muscle, liver, pancreas (head and tail), fat (perinephric and subcutaneous), kidney (cortex and medulla), prostate, stomach, ileum, jejunum, colon, adrenal gland, and spleen. We found that the majority of these tissues expressed alpha 2C10, with the exceptions being the head of the pancreas, subcutaneous fat, colon, and spleen. In marked distinction to other studies, however, we found a prolific expression of the alpha 2C4 and alpha 2C2 subtypes. Expression of alpha 2C4 was found in all tissues with the exception of liver, fat, stomach, and colon, and a virtually ubiquitous expression of alpha 2C2 was found, with the exception of epicardium. Of all tissues studied, only colon and subcutaneous fat expressed a single alpha 2AR subtype, which was alpha 2C2. Thus, the alpha 2AR subtypes do not have a confined expression but

  11. Accumulation of CCR4⁺CTLA-4 FOXP3⁺CD25(hi regulatory T cells in colon adenocarcinomas correlate to reduced activation of conventional T cells.

    Directory of Open Access Journals (Sweden)

    Helena Svensson

    Full Text Available BACKGROUND: Colorectal cancer usually gives rise to a specific anti-tumor immune response, but for unknown reasons the resulting immunity is not able to clear the tumor. Recruitment of activated effector lymphocytes to the tumor is important for efficient anti-tumor responses, while the presence of regulatory T cells (Treg down-modulate tumor-specific immunity. We therefore aimed to determine homing mechanisms and activation stage of Treg and effector T cell infiltrating colon tumors compared to cells from the unaffected mucosa in patients suffering from colon adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Lymphocytes were isolated from unaffected and tumor mucosa from patients with colon adenocarcinoma, and flow cytometry, immunohistochemistry, and quantitative PCR was used to investigate the homing mechanisms and activation stage of infiltrating Treg and conventional lymphocytes. We detected significantly higher frequencies of CD25(highFOXP3⁺CD127(low putative Treg in tumors than unaffected mucosa, which had a complete demethylation in the FOXP3 promotor. Tumor-associated Treg had a high expression of CTLA-4, and some appeared to be antigen experienced effector/memory cells based on their expression of αEβ7 (CD103. There were also significantly fewer activated T cells and more CTLA-4⁺ conventional T cells susceptible to immune regulation in the tumor-associated mucosa. In contrast, CD8⁺granzyme B⁺ putative cytotoxic cells were efficiently recruited to the tumors. The frequencies of cells expressing α4β7 and the Th1 associated chemokine receptor CXCR3 were significantly decreased among CD4⁺ T cells in the tumor, while frequencies of CD4⁺CCR4⁺ lymphocytes were significantly increased. CONCLUSIONS/SIGNIFICANCE: This study shows that CCR4⁺CTLA4(hi Treg accumulate in colon tumors, while the frequencies of activated conventional Th1 type T cells are decreased. The altered lymphocyte composition in colon tumors will probably

  12. The role of stromal mast cells in the modification of CD4 CD25 Foxp3 regulatory T cells, Th17 lymphocytes and cytotoxic lymphocytes Tc1 in the development and progression of tumor

    OpenAIRE

    Katarzyna Starska; Ewa Brzezińska-Błaszczyk

    2010-01-01

    Despite the lack of direct evidence that immune surveillance cells protect against tumor development, indirect clinical observations and experimental studies indicate activity in the immune response against cancer cells of various origin. Little is known about the effects of the stromal tumor mast cell (MC) in the activity of immune cells, i.e. CD4[sup] [/sup]CD25[sup] [/sup]Foxp3[sup] [/sup] regulatory T cells, Th17 lymphocytes, cytotoxic lymphocytes Tc1 and their mutual modulatory function ...

  13. Ligand chain length conveys thermochromism.

    Science.gov (United States)

    Ganguly, Mainak; Panigrahi, Sudipa; Chandrakumar, K R S; Sasmal, Anup Kumar; Pal, Anjali; Pal, Tarasankar

    2014-08-14

    Thermochromic properties of a series of non-ionic copper compounds have been reported. Herein, we demonstrate that Cu(II) ion with straight-chain primary amine (A) and alpha-linolenic (fatty acid, AL) co-jointly exhibit thermochromic properties. In the current case, we determined that thermochromism becomes ligand chain length-dependent and at least one of the ligands (A or AL) must be long chain. Thermochromism is attributed to a balanced competition between the fatty acids and amines for the copper(II) centre. The structure-property relationship of the non-ionic copper compounds Cu(AL)2(A)2 has been substantiated by various physical measurements along with detailed theoretical studies based on time-dependent density functional theory. It is presumed from our results that the compound would be a useful material for temperature-sensor applications. PMID:24943491

  14. Review of alpha_s determinations

    CERN Document Server

    Pich, Antonio

    2013-01-01

    The present knowledge on the strong coupling is briefly summarized. The most precise determinations of alpha_s, at different energies, are reviewed and compared at the Z mass scale, using the predicted QCD running. The impressive agreement achieved between experimental measurements and theoretical predictions constitutes a beautiful and very significant test of Asymptotic Freedom, establishing QCD as the fundamental theory of the strong interaction. The world average value of the strong coupling is found to be alpha_s(M_Z^2)= 0.1186 \\pm 0.0007.

  15. Interaction of indoleamine 2, 3-dioxygenase and CD4 + CD25 + Foxp3 + regulatory T cell in asthmatic mice%IDO与Treg在支气管哮喘小鼠中的相互作用及其意义

    Institute of Scientific and Technical Information of China (English)

    周丽蓉; 张劼; 罗永艾

    2013-01-01

    Objective To explore the interaction and the role of indoleamine 2,3-dioxygenase (IDO) and CD4 + CD25 + Foxp3 + regulatory T cell (Treg) in a mice model of allergic bronchial asthma.Methods BALB/c mice were sensitized and challenged by ovalbumin (OVA).Penh were measured to evaluate the airway responsiveness by noninvasive lung functional instrument.Bronchoalveolar lavage cytology was analyzed.IFN-γ,IL-4 and IL-10 in BALF were detected by enzyme-linked immunosorbent assay (ELISA).The mRNA expression of IDO and Foxp3 was measured by real-time fluorescence-based quantitative PCR.The protein expression of IDO was detected by immunohistochemistry.The percentage of Treg in CD4 + cells was assessed by flow cytometry.Results The airway responsiveness,the total cell number,the eosinophils and IL-4 in BALF of the asthmatic group significantly increased as compared with the control group (P < 0.01).The levels of IFN-γand IL-10 in BALF,the mRNA expression of IDO and Foxp3,the protein expression of IDO,and the percentage of Treg in CD4 + cells in the asthmatic group were significantly lower than those in the control group (P <0.01).The mRNA expression of IDO and Foxp3 was positively correlated with each other (r =0.819,0.807,P <0.05).The protein expression of IDO was positively correlated with the percentage of Treg in CD4 +cells (r =0.783,0.765,P < 0.05).Conclusions IDO and Treg reciprocally regulate each other,which surmounts immune tolerance and induces asthma.Therefore,IDO and Treg may play important roles in asthma.%目的 探讨吲哚胺2,3双加氧酶(indoleamine 2,3-dioxygense,IDO)与CD4+ CD25+ Foxp3+调节性T细胞(Treg)之间的相关性及在支气管哮喘发病机制中的作用.方法 BALB/c小鼠用随机数字表法分成对照组和哮喘组,每组8只.哮喘组以鸡卵清蛋白(ovalbumin,OVA)致敏,激发小鼠建立哮喘模型,无创肺功能仪检测气道反应性,支气管肺泡灌洗液(BALF)进行细胞学分析,ELISA检测BALF

  16. Catch Chain

    OpenAIRE

    Talbert, Robert

    2010-01-01

    Catch Chain is a book of poems that traces the journey of a Corrections Officer who attempts to combat issues of isolation, inhumane treatment of inmates and societal rejection in jails by embarking upon a cross-country road trip. However, the same issues the officer initially wrestled with begin cropping up in different cities, on various highways and in a multitude of states. The excitement and adventure of the open road runs parallel to the recurring imprisonment of the guard's mind.

  17. Alpha-thalassemia mutations in Gilan Province, North Iran.

    Science.gov (United States)

    Hadavi, Valeh; Jafroodi, Maryam; Hafezi-Nejad, Nima; Moghadam, Sousan Dehnadi; Eskandari, Fatemeh; Tarashohi, Shahin; Pourfahim, Hamideh; Oberkanins, Christian; Law, Hai-Yang; Najmabadi, Hossein

    2009-01-01

    One hundred and three patients from Gilan Province, Iran, presenting with hypochromic and microcytic anemia parameters without iron deficiency were included in this study. Using gap-polymerase chain reaction (gap-PCR), reverse hybridization StripAssay and DNA sequencing, we detected a total of 113 alpha-globin mutations in 94 (91.3%) of these patients. Most prevalent of the 16 different alpha-thalassemia (alpha-thal) alleles was -alpha(3.7) (42.5%), followed by the polyadenylation signal (poly A2) (AATAAA>AATGAA) (12.4%), Hb Constant Spring [Hb CS, alpha142, Term-->Gln (TAA>CAA in alpha2] (10.6%), --(MED) (8.8%), IVS-I donor site [GAG GTG AGG>GAG G-----, alpha(-5 nt) (-TGAGG)] (7.1%), -alpha(4.2) (4.4%) and poly A1 (AATAAA>AATAAG) (3.5%). An additional nine mutations were observed at frequencies below 2%. We also found two novel alpha1 gene mutations: alpha(-9) (HBA1: c.-9 G>C) and alpha(IVS-I-4) (HBA1: c.95+4 A>G). Our new findings will be valuable for improving targeted thalassemia screening and prevention strategies in this area. PMID:19657838

  18. Increased cardiac alpha-myosin heavy chain in left atria and decreased myocardial insulin-like growth factor (Igf-I) expression accompany low heart rate in hibernating grizzly bears.

    Science.gov (United States)

    Barrows, N D; Nelson, O L; Robbins, C T; Rourke, B C

    2011-01-01

    Grizzly bears (Ursus arctos horribilis) tolerate extended periods of extremely low heart rate during hibernation without developing congestive heart failure or cardiac chamber dilation. Left ventricular atrophy and decreased left ventricular compliance have been reported in this species during hibernation. We evaluated the myocardial response to significantly reduced heart rate during hibernation by measuring relative myosin heavy-chain (MyHC) isoform expression and expression of a set of genes important to muscle plasticity and mass regulation in the left atria and left ventricles of active and hibernating bears. We supplemented these data with measurements of systolic and diastolic function via echocardiography in unanesthetized grizzly bears. Atrial strain imaging revealed decreased atrial contractility, decreased expansion/reservoir function (increased atrial stiffness), and decreased passive-filling function (increased ventricular stiffness) in hibernating bears. Relative MyHC-α protein expression increased significantly in the atrium during hibernation. The left ventricle expressed 100% MyHC-β protein in both groups. Insulin-like growth factor (IGF-I) mRNA expression was reduced by ∼50% in both chambers during hibernation, consistent with the ventricular atrophy observed in these bears. Interestingly, mRNA expression of the atrophy-related ubiquitin ligases Muscle Atrophy F-box (MAFBx) and Muscle Ring Finger 1 did not increase, nor did expression of myostatin or hypoxia-inducible factor 1α (HIF-1α). We report atrium-specific decreases of 40% and 50%, respectively, in MAFBx and creatine kinase mRNA expression during hibernation. Decreased creatine kinase expression is consistent with lowered energy requirements and could relate to reduced atrial emptying function during hibernation. Taken together with our hemodynamic assessment, these data suggest a potential downregulation of atrial chamber function during hibernation to prevent fatigue and dilation

  19. Review of alpha_s determinations

    OpenAIRE

    Pich, Antonio

    2013-01-01

    The present knowledge on the strong coupling is briefly summarized. The most precise determinations of alpha_s, at different energies, are reviewed and compared at the Z mass scale, using the predicted QCD running. The impressive agreement achieved between experimental measurements and theoretical predictions constitutes a beautiful and very significant test of Asymptotic Freedom, establishing QCD as the fundamental theory of the strong interaction. The world average value of the strong coupl...

  20. 3$\\alpha$-cluster structure and monopole transition in $^{12}$C and $^{14}$C

    CERN Document Server

    Yoshida, Yuta

    2016-01-01

    3$\\alpha$-cluster structures and monopole transitions of $0^+$ states in $^{12}$C and $^{14}$C were investigated with $3\\alpha$- and $^{10}$Be+$\\alpha$-cluster models. A gas-like $3\\alpha$ state and a bending-chain $3\\alpha$ state were obtained in the $0^+_2$ and $0^+_3$ states of $^{12}$C, respectively. In $^{14}$C, a linear-chain 3$\\alpha$ structure is found in the $0^+_4$ state near the $^{10}$Be+$\\alpha$ threshold, but a cluster gas-like state does not appear because valence neutrons attract $\\alpha$ clusters and suppress spatial development of 3$\\alpha$ clustering. It was found that the linear-chain state in $^{14}$C is stabilized against the bending and $\\alpha$ escaping modes by valence neutrons. The monopole transition strengths in $^{12}$C are enhanced by $3\\alpha$-cluster developing, whereas, those in $^{14}$C are not enhanced so much because of the tight binding o