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Sample records for alpha chain cd25

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. Iron modulates the alpha chain of fibrinogen.

    Science.gov (United States)

    Nielsen, Vance G; Jacobsen, Wayne K

    2016-04-01

    Iron-bound fibrinogen has been noted to accelerate plasmatic coagulation in patients with divergent conditions involving upregulation of heme oxygenase activity, including hemodialysis, Alzheimer's disease, sickle cell anemia, and chronic migraine. Our goal was to determine if a site of iron-fibrinogen interaction was on the alpha chain. Using thrombelastography, we compared the coagulation kinetic profiles of plasma exposed to 0-10 µM ferric chloride after activation of coagulation with thrombin generated by contact activation of plasma with the plastic sample cup or by exposure to 1 µg/ml of Calloselasma rhodostoma venom (rich in ancrod activity), which causes coagulation via polymerization of alpha chain monomers. Venom mediated coagulation always occurred before thrombin activated thrombus formation, and ferric chloride always diminished the time of onset of coagulation and increased the velocity of clot growth. Iron enhances plasmatic coagulation kinetics by modulating the alpha chain of fibrinogen.

  5. 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

    . Upon enteroantigen activation, the CD4+ CD25- T cells secrete IL-4, IL-5, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-alpha and IFN-gamma. Clonotype mapping of the TCRBV regions 1-18 of enteroantigen-reactive CD4+ CD25- T cells by TCR clonotype mapping revealed...

  6. HB Hillingdon [alpha46(CE4)Phe-->Val (alpha1 Or alpha2)]: a new alpha chain hemoglobin variant.

    Science.gov (United States)

    Babb, Anna; Solaiman, Susannah; Green, Brian N; Mantio, Debbie; Patel, Ketan

    2009-01-01

    Routine antenatal hemoglobinopathy screening detected a new alpha chain variant that eluted with Hb A(2) on cation exchange high performance liquid chromatography (HPLC) in a lady of Sri Lankan origin who had normal hematological indices. The mutation was identified by electrospray ionization mass spectrometry (ESI-MS) as alpha46(CE4)Phe-->Val, inferring that the variant was due to a single base change at codon 46 (TTC>GTC) of the alpha1- or alpha2-globin genes.

  7. Alpha decay chains from superheavy nuclei

    CERN Document Server

    Samanta, C

    2008-01-01

    Magic islands for extra-stable nuclei in the midst of the sea of fission-instability were predicted to be around Z=114, 124 or, 126 with N=184, and Z=120, with N=172. Whether these fission-survived superheavy nuclei with high Z and N would live long enough for detection or, undergo alpha-decay in a very short time remains an open question. Alpha-decay half lives of nuclei with 130 118 are found to have alpha-decay half lives of the order of microseconds or, less.

  8. Collagen alpha5 and alpha2(IV) chain coexpression: analysis of skin biopsies of Alport patients.

    Science.gov (United States)

    Patey-Mariaud de Serre, N; Garfa, M; Bessiéres, B; Noël, L H; Knebelmann, B

    2007-08-01

    Alport syndrome is a collagen type IV disease caused by mutations in the COL4A5 gene with the X-linked form being most prevalent. The resultant alpha5(IV) collagen chain is a component of the glomerular and skin basement membranes (SBMs). Immunofluorescent determination of the alpha5(IV) chain in skin biopsies is the procedure of choice to identify patients. In 30% of patients, however, the mutant protein is still found in the SBM resulting in a normal staining pattern. In order to minimize or eliminate false results, we compared the distribution of the alpha2(IV) chain (another SBM component) and the alpha5(IV) chain by standard double label immunofluorescence (IF) and by confocal laser scanning microscopy. The study was performed on 55 skin biopsies of patients suspected of Alports and five normal control specimens. In normal skin, IF showed the classical linear pattern for both collagens along the basement membrane. Additionally, decreased alpha5(IV) was found in the bottom of the dermal papillary basement membrane. Confocal analysis confirmed the results and show alpha5(IV) focal interruptions. In suspected patients, both techniques showed the same rate of abnormal alpha5(IV) expression: segmental in women and absent in men. Our results show a physiological variation of alpha5(IV) location with focal interruptions and decreased expression in the bottom of the dermal basement membrane. Comparison of alpha5(IV) with alpha2(IV) expression is simple and eliminates technical artifacts.

  9. In ovo injection of anti-chicken CD25 monoclonal antibodies depletes CD4+CD25+ T cells in chickens.

    Science.gov (United States)

    Shanmugasundaram, Revathi; Selvaraj, Ramesh K

    2013-01-01

    The CD4(+)CD25(+) cells have T regulatory cell properties in chickens. This study investigated the effect of in ovo injection of anti-chicken CD25 monoclonal antibodies (0.5 mg/egg) on CD4(+)CD25(+) cell depletion and on amounts of interleukin-2 mRNA and interferon-γ mRNA in CD4(+)CD25(-) cells posthatch. Anti-chicken CD25 or PBS (control) was injected into 16-d-old embryos. Chicks hatched from eggs injected with anti-chicken CD25 antibodies had a lower CD4(+)CD25(+) cell percentage in the blood until 25 d posthatch. The anti-chicken CD25 antibody injection nearly depleted CD4(+)CD25(+) cells in the blood until 16 d posthatch. At 30 d posthatch, the CD4(+)CD25(+) cell percentage in the anti-CD25-antibody-injected group was comparable with the percentage in the control group. At 16 d posthatch, the anti-chicken CD25 antibody injection decreased CD4(+)CD25(+) cell percentages in the thymus, spleen, and cecal tonsils. Chickens hatched from anti-CD25-antibody-injected eggs had approximately 25% of CD4(+)CD25(+) cells in the cecal tonsils and thymus compared with those in the cecal tonsils and thymus of the control group. The CD4(+)CD25(-) cells from the spleen and cecal tonsils of chicks hatched from anti-chicken-CD25-injected eggs had higher amounts of interferon-γ and interleukin-2 mRNA than CD4(+)CD25(-) cells from the control group. It could be concluded that injecting anti-chicken CD25 antibodies in ovo at 16 d of incubation nearly depleted the CD4(+)CD25(+) cells until 25 d posthatch.

  10. Collagen IV alpha 3, alpha 4, and alpha 5 chains in rodent basal laminae: sequence, distribution, association with laminins, and developmental switches

    OpenAIRE

    1994-01-01

    Collagen IV is a major component of vertebrate basal laminae (BLs). Studies in humans have revealed a family of genes encoding alpha 1- alpha 6 collagen IV chains and implicated alpha 3-alpha 6 in disease processes (Goodpasture and Alport syndromes and diffuse leiomyomatosis). To extend studies of these components to an experimentally accessible animal, we cloned cDNAs encoding partial collagen alpha 3, alpha 4, and alpha 5(IV) chains from the mouse. Ribonuclease protection assays showed that...

  11. Daily subcutaneous injections of peptide induce CD4+ CD25+ T regulatory cells.

    Science.gov (United States)

    Dahlberg, P E; Schartner, J M; Timmel, A; Seroogy, C M

    2007-08-01

    Peptide immunotherapy is being explored to modulate varied disease states; however, the mechanism of action remains poorly understood. In this study, we investigated the ability of a subcutaneous peptide immunization schedule to induce of CD4(+) CD25(+) T regulatory cells. DO11.10 T cell receptor (TCR) transgenic mice on a Rag 2(-/-) background were injected subcutaneously with varied doses of purified ovalbumin (OVA(323-339)) peptide daily for 16 days. While these mice have no CD4(+) CD25(+) T regulatory cells, following this injection schedule up to 30% of the CD4(+) cells were found to express CD25. Real-time quantitative polymerase chain reaction (QPCR) analysis of the induced CD4(+) CD25(+) T cells revealed increased expression of forkhead box P3 (FoxP3), suggesting that these cells may have a regulatory function. Proliferation and suppression assays in vitro utilizing the induced CD4(+) CD25(+) T cells revealed a profound anergic phenotype in addition to potent suppressive capability. Importantly, co-injection of the induced CD4(+) CD25(+) T cells with 5,6-carboxy-succinimidyl-fluorescence-ester (CFSE)-labelled naive CD4(+) T cells (responder cells) into BALB/c recipient mice reduced proliferation and differentiation of the responder cells in response to challenge with OVA(323-339) peptide plus adjuvant. We conclude that repeated subcutaneous exposure to low-dose peptide leads to de novo induction of CD4(+) CD25(+) FoxP3(+) T regulatory cells with potent in vitro and in vivo suppressive capability, thereby suggesting that one mechanism of peptide immunotherapy appears to be induction of CD4(+) CD25(+) Foxp3(+) T regulatory cells.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Separation of the subtypes of type V collagen molecules, [alpha 1(V)]2 alpha 2(V) and alpha 1(V) alpha 2(V) alpha 3(V), by chain composition-dependent affinity for heparin: single alpha 1(V) chain shows intermediate heparin affinity between those of the type V collagen subtypes composed of [alpha 1(V)]2 alpha 2(V) and of alpha 1(V) alpha 2(V) alpha 3(V).

    Science.gov (United States)

    Mizuno, K; Hayashi, T

    1996-11-01

    The heparin affinities of heat-treated type V collagen alpha-chains and the triple-helical molecules were evaluated in terms of the NaCl concentration required for prevention of binding to a heparin-Sepharose column. After heat treatment, alpha 1(V) chain required approximately two-fold higher NaCl concentration to pass through the column than the other two chains, alpha 2(V) and alpha 3(V). Thus, the heparin affinity of alpha 1(V) may be approximately two-fold higher than those of the other alpha (V)-chains. The type V collagen molecules in triple-helical conformation were separated into two fractions at 170 mM NaCl in 20 mM phosphate buffer, pH 7.2, containing 2 M urea; bound and non-bound. The ratio of the three alpha-chains, alpha 1(V): alpha 2(V): alpha 3(V) was 2 : 1 : 0 and 1 : 1 : 1 in the bound and flow-through fractions, respectively, on analysis by SDS-PAGE. The differential affinity of the two fractions could be accounted for by the number of alpha 1(V) chains in the triple-helical molecule, if these fractions contained triple-helical subtypes with the chain compositions of [alpha 1(V)]2 alpha 2(V) and alpha 1(V) alpha 2(V) alpha 3(V), respectively. From the comparison of the NaCl concentration required for prevention of the binding, [alpha 1(V)]2, alpha 2(V) had about two-fold higher affinity than alpha 1(V) alpha 2(V) alpha 3(V), and the separated alpha 1(V) chain showed an intermediate affinity. A possible explanation for difference in heparin affinity among the subtypes of molecules and the separated alpha-chains is that the heparin affinity of type V collagen molecule is governed by the number of alpha 1(V) chains contained in the molecule and that steric restraint in a triple-helical conformation weakens the binding of alpha 1(V) chain to heparin.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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

  17. Laminin alpha2 chain-deficient congenital muscular dystrophy: variable epitope expression in severe and mild cases

    DEFF Research Database (Denmark)

    Cohn, R D; Herrmann, R; Sorokin, L;

    1998-01-01

    To characterize the expression of distinct fragments of laminin alpha2 chain in patients with partial laminin alpha2 chain deficiency and variable clinical severity.......To characterize the expression of distinct fragments of laminin alpha2 chain in patients with partial laminin alpha2 chain deficiency and variable clinical severity....

  18. [A new alpha chain of jacalin from two wild species of jack-fruit seeds].

    Science.gov (United States)

    Ngoc, L D; Brillard, M; Hoebeke, J; Aucouturier, P

    1995-02-01

    Jacalins, from jack-fruit seeds of 2 wild species (Artocarpus asperulus, Artocarpus masticata) were purified by mucine-sepharose 4B affinity chromatography. The alpha and beta chains were separated by reverse phase high pressure liquid chromatography (HPLC). Analysis by HPLC with a C8 column and the determination of the N-terminal sequence of the alpha-chain of these jacalins allowed the identification of a new alpha-chain. Immunological cross-reactivity and carbohydrate specificity indicate that jacalins possessing the new alpha-chain conserve structural and functional properties of the other members of Artocarpus genus.

  19. Effects of in vivo injection of anti-chicken CD25 monoclonal antibody on regulatory T cell depletion and CD4+CD25- T cell properties in chickens.

    Science.gov (United States)

    Shanmugasundaram, Revathi; Selvaraj, Ramesh K

    2012-03-01

    Regulatory T cells (Tregs) are defined as CD4(+)CD25(+) cells in chickens. This study examined the effects of an anti-chicken CD25 monoclonal antibody injection (0.5 mg/bird) on in vivo depletion of Tregs and the properties of CD4(+)CD25(-) cells in Treg-depleted birds. The CD4(+)CD25(+) cell percentage in the blood was lower at 8 d post injection than at 0 d. Anti-CD25-mediated CD4(+)CD25(+) cell depletion in blood was maximum at 12 d post injection. The anti-CD25 antibody injection depleted CD4(+)CD25(+) cells in the spleen and cecal tonsils, but not in the thymus, at 12 d post antibody injection. CD4(+)CD25(-) cells from the spleen and cecal tonsils of birds injected with the anti-chicken CD25 antibody had higher proliferation and higher IL-2 and IFNγ mRNA amounts than the controls at 12 d post injection. At 20 d post injection, CD4(+)CD25(+) cell percentages in the blood, spleen and thymus were comparable to that of the 0 d post injection. It could be concluded that anti-chicken CD25 injection temporarily depleted Treg population and increased and IL-2 and IFNγ mRNA amounts in CD4(+)CD25(-) cells at 12d post injection.

  20. Collagen polymorphism: characterization of molecules with the chain composition (alpha 1 (3)03 in human tissues.

    Science.gov (United States)

    Chung, E; Miller, E J

    1974-03-01

    Collagen moleculess with the chain comizposition [alpha1(III)](3), have been isolated from pepsin-solubilized collagen of dermis, aorta, and leiomlyoma of the uterus by differential salt precipitation. On denaturation, approximately 90 percent of this collagen is recovered as a gamma component (300,000 daltons). Reduction and alkylation of the high-molecular-weight component yields alpha1(III) chains (95,000 daltons). In addition to containing cysteine, alpha1(III) chains exhibit several other compositional differences when compared to alpha1(I), alpha1(II), or alpha2 chains from human tissues.

  1. Distribution of basement membrane type IV collagen alpha chains in ameloblastoma: an immunofluorescence study

    OpenAIRE

    Nakano, K.; Siar, C. H.; Nagai, N.; Naito, I.; Sado, Y.; Nagatsuka, H; Hoh, C; Kurada, K.; Tsujigiwa, H; M. Gunduz

    2002-01-01

    Background: Type IV collagen, a heterotrimeric molecule that exists in six genetically distinct forms, alpha1(IV)-alpha6(IV) is a major structural component of basement membrane (BM) and acts as a scaffold for other BM constituents. Methods: Indirect immunofluorescence using alpha chain-specific monoclonal antibodies was employed to clarify basement membrane (BM) collagen IV distribution in two ameloblastoma, and for comparison, on oral mucosa and tooth germ. Results: Ameloblastoma BM express...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  3. Comparative distribution of the alpha 1(IV), alpha 5(IV), and alpha 6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients.

    OpenAIRE

    Peissel, B; Geng, L.; Kalluri, R.; Kashtan, C; Rennke, H G; Gallo, G R; Yoshioka, K.; Sun, M J; Hudson, B.G.; Neilson, E. G.

    1995-01-01

    We have shown previously that the 5' ends of the genes for the alpha 5(IV) and alpha 6(IV) collagen chains lie head-to-head on Xq22 and are deleted in patients with Alport syndrome (AS)-associated diffuse leiomyomatosis. In this study, we raised a rabbit anti-human alpha 6(IV)chain antibody, demonstrated its specificity by the analysis of recombinant NC1 domains af all six type IV chains, and studied the distribution of the alpha 6(IV) chain in relation to the alpha 1(IV) and alpha 5(IV) chai...

  4. 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.

  5. Increased numbers of IL-7 receptor molecules on CD4+CD25-CD107a+ T-cells in patients with autoimmune diseases affecting the central nervous system.

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    Nalini Kumar Vudattu

    Full Text Available BACKGROUND: High content immune profiling in peripheral blood may reflect immune aberrations associated with inflammation in multiple sclerosis (MS and other autoimmune diseases affecting the central nervous system. METHODS AND FINDINGS: Peripheral blood mononuclear cells from 46 patients with multiple sclerosis (MS, 9 patients diagnosed with relapsing remitting MS (RRMS, 13 with secondary progressive multiple sclerosis (SPMS, 9 with other neurological diseases (OND and well as 15 healthy donors (HD were analyzed by 12 color flow cytometry (TCRalphabeta, TCRgammadelta, CD4, CD8alpha, CD8beta, CD45RA, CCR7, CD27, CD28, CD107a, CD127, CD14 in a cross-sectional study to identify variables significantly different between controls (HD and patients (OND, RRMS, SPMS. We analyzed 187 individual immune cell subsets (percentages and the density of the IL-7 receptor alpha chain (CD127 on 59 individual immune phenotypes using a monoclonal anti-IL-7R antibody (clone R34.34 coupled to a single APC molecule in combination with an APC-bead array. A non-parametric analysis of variance (Kruskal-Wallis test was conducted in order to test for differences among the groups in each of the variables. To correct for the multiplicity problem, the FDR correction was applied on the p-values. We identified 19 variables for immune cell subsets (percentages which allowed to segregate healthy individuals and individuals with CNS disorders. We did not observe differences in the relative percentage of IL-7R-positive immune cells in PBMCs. In contrast, we identified significant differences in IL-7 density, measured on a single cell level, in 2/59 variables: increased numbers of CD127 molecules on TCRalphabeta+CD4+CD25 (intermed T-cells and on TCRalphabeta+CD4+CD25-CD107a+ T-cells (mean: 28376 Il-7R binding sites on cells from HD, 48515 in patients with RRMS, 38195 in patients with SPMS and 33692 IL-7 receptor binding sites on cells from patients with OND. CONCLUSION: These data

  6. Expansion of CD25+ Innate Lymphoid Cells Reduces Atherosclerosis

    Science.gov (United States)

    Engelbertsen, Daniel; Foks, Amanda C.; Alberts-Grill, Noah; Kuperwaser, Felicia; Chen, Tao; Lederer, James A.; Jarolim, Petr; Grabie, Nir; Lichtman, Andrew H.

    2015-01-01

    Objective Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results We demonstrate that CD25+ ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr−/−rag1−/− mice. To investigate the role of ILCs in atherosclerosis, ldlr−/−rag1−/− mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or with IL-2/anti-IL-2 complexes that expand CD25+ ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti-IL-2 -treated mice. These IL-2 treated mice had reduced VLDL cholesterol and increased triglycerides compared to controls and reduced apolipoprotein B100 gene expression in the liver. IL-2/anti-IL-2 treatment caused expansion of ILC2s in aorta and other tissues, elevated levels of IL-5, systemic eosinophila and hepatic eosinophilic inflammation. Blockade of IL-5 reversed the IL-2-complex-induced eosinophilia but did not change lesion size. Conclusions This study demonstrates that expansion of CD25-expressing ILCs by IL-2/anti-IL-2 complexes leads to a reduction in VLDL cholesterol and atherosclerosis. Global depletion of ILCs by anti-CD90.2 did not significantly affect lesion size indicating that different ILC subsets may have divergent effects on atherosclerosis. PMID:26494229

  7. Regulation of hepatic branched-chain alpha-keto acid dehydrogenase complex in rats fed a high-fat diet

    Science.gov (United States)

    Objective: Branched-chain alpha-keto acid dehydrogenase complex (BCKDC) regulates branched-chain amino acid (BCAA) metabolism at the level of branched chain alpha-ketoacid (BCKA) catabolism. It has been demonstrated that the activity of hepatic BCKDC is markedly decreased in type 2 diabetic animal...

  8. CD4+CD25+ regulatory T lymphocytes in tuberculous pleural effusion

    Institute of Scientific and Technical Information of China (English)

    QIN Xue-jun; SHI Huan-zhong; LIANG Qiu-li; HUANG Lu-ying; YANG Hai-bo

    2008-01-01

    Background Active suppression by CD4+CD25+ regulatory T lymphocytes plays an important role in the down-regulation of T cell responses to foreign and self-antigens.This study was conducted to analyze whether the CD4+CD25+ regulatory T cells exist and function normally in tuberculous pleural effusion.Methods The percentages of CD4+CD25+ T cells in pleural effusion and peripheral blood from patients with tuberculous pleurisy and peripheral blood from healthy control subjects were determined by flow cytometry.The expression of forkhead transcription factor Foxp3 was also examined.CD4+CD25+ and CD4+CD25- T cells from pleural effusion and blood were isolated,and were cultured to observe the effects Of CD4+CD25+ T cells on proliferation response of CD4+CD25- T cells in Vitro.Results There were increased numbers of CD4+CD25+ T cells in tuberculous pleural effusion compared with peripheral blood from both patients with tuberculous pleurisy and normal subjects,and these cells demonstrated a constitutive high-level expression of Foxp3.Moreover,CD4+CD25+ T cells mediated potent inhibition of proliferation response of CD4+CD25- T cells.Conclusion The increased CD4+CD25+ T cells in tuberculous pleu ral effusion express a high level of Foxp3 transcription factor,while potently suppressing the proliferation of CD4+CD25- T cells.

  9. Phenotypes and clinical significance of circulating CD4+CD25+ regulatory T cells (Tregs in patients with acute-on-chronic liver failure (ACLF

    Directory of Open Access Journals (Sweden)

    Yang Jiezuan

    2012-09-01

    Full Text Available Abstract Background CD4+CD25+ regulatory T cells (Tregs play an important role in maintaining immunological tolerance to self and foreign antigens. T cell receptors (TCR reflect the composition and function of T cells. It is not universally agreed that there is a relationship between CD4+CD25+ Treg frequency and the severity of acute-on-chronic liver failure (ACLF. The repertoire of TCR beta chain variable (TCRBV regions of peripheral Tregs in ACLF patients is not well understood. Methods Human PBMCs were separated and sorted into CD4+CD25+ Treg subsets using density gradient centrifugation and magnetic activated cell sorting (MACS. The CD4+CD25high Treg frequency in peripheral blood of ACLF and chronic hepatitis B (CHB patients was measured by flow cytometry. The molecular profiles of TCRBV CDR3 were determined using gene melting spectral pattern (GMSP analysis. TCRBV gene families were cloned and sequenced when the GMSP profiles showed a single-peak. Results CD4+CD25high Treg prevalence in peripheral blood of ACLF patients is increased significantly compared to healthy donors (HDs (P P +CD25high Tregs in ACLF or CHB patients is positively correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most prevalent TCRBV in CD4+CD25+ Tregs in ACLF and CHB patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families. Conclusions The CD4+CD25high Tregs prevalence in peripheral blood is indicative of disease severity in ACLF or CHB patients. The relatively conserved TCRBV20 CDR3 motif “TGTGHSPLH” and TCRBV11 CDR3 motif “VYNEQ” may be used in helping diagnosis and treat patients with ACLF.

  10. A new alpha chain hemoglobin variant: Hb Al-Hammadi Riyadh [alpha75(EF4)Asp-->Val (alpha2)].

    Science.gov (United States)

    Burnichon, Nelly; Lacan, Philippe; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Mowafy, Mohammed; Couprie, Nicole; Francina, Alain

    2006-01-01

    A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh [codon 75 (GAC-->GTC); alpha75(EF4)Asp-->Val (alpha2)] corresponding to an A-->T transversion on the second exon of the alpha2-globin gene, is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). The variant was found during a routine Hb analysis for anemia in a 16-month-old boy who lived in Riyadh, Kingdom of Saudi Arabia.

  11. 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.

  12. 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...

  13. 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.

  14. Integrin alpha chains exhibit distinct temporal and spatial localization patterns in epithelial cells of the Drosophila ovary.

    Science.gov (United States)

    Dinkins, Michael B; Fratto, Victoria M; Lemosy, Ellen K

    2008-12-01

    Integrins are heterodimeric transmembrane receptors that modulate cell adhesion, migration, and signaling. Multiple integrin chains contribute to development and morphogenesis of a given tissue. Here, we analyze the expression of Drosophila integrin alpha chains in the ovarian follicular epithelium, a model for tissue morphogenesis and cell migration. We find expression throughout development of the beta chain, betaPS. Alpha chains, however, exhibit both spatial and temporal expression differences. alphaPS1 and alphaPS2 integrins are detected during early and mid-oogenesis on apical, lateral, and basal membranes with the betaPS chain, whereas alphaPS3-family integrins (alphaPS3, alphaPS4, alphaPS5) are expressed in anterior cells late in oogenesis. Surprisingly, we find that alphaPS3-family integrins are dispensable for dorsal appendage morphogenesis but play a role in the final length of the egg, suggesting redundant functions of integrins in a simple tissue. We also demonstrate roles for alphaPS3betaPS integrin in border cell migration and in stretch cells.

  15. Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis.

    Science.gov (United States)

    Uhlig, Holm H; Coombes, Janine; Mottet, Christian; Izcue, Ana; Thompson, Claire; Fanger, Andrea; Tannapfel, Andrea; Fontenot, Jason D; Ramsdell, Fred; Powrie, Fiona

    2006-11-01

    CD4+CD25+ regulatory T cells can prevent and resolve intestinal inflammation in the murine T cell transfer model of colitis. Using Foxp3 as a marker of regulatory T cell activity, we now provide a comprehensive analysis of the in vivo distribution of Foxp3+CD4+CD25+ cells in wild-type mice, and during cure of experimental colitis. In both cases, Foxp3+CD4+CD25+ cells were found to accumulate in the colon and secondary lymphoid organs. Importantly, Foxp3+ cells were present at increased density in colon samples from patients with ulcerative colitis or Crohn's disease, suggesting similarities in the behavior of murine and human regulatory cells under inflammatory conditions. Cure of murine colitis was dependent on the presence of IL-10, and IL-10-producing CD4+CD25+ T cells were enriched within the colon during cure of colitis and also under steady state conditions. Our data indicate that although CD4+CD25+ T cells expressing Foxp3 are present within both lymphoid organs and the colon, subsets of IL-10-producing CD4+CD25+ T cells are present mainly within the intestinal lamina propria suggesting compartmentalization of the regulatory T cell response at effector sites.

  16. Thermodynamic aspects of calcium binding by poly({alpha}-L-guluronate) chains. A molecular simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Plazinski, Wojciech, E-mail: wojtek@vega.umcs.lublin.pl [Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, ul. Niezapominajek 8, 30-239 Cracow (Poland); Drach, Mateusz [Department of Theoretical Chemistry, Faculty of Chemistry, UMCS, pl. M. Curie-Sklodowskiej 3, 20-031 Lublin (Poland)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer The molecular dynamics studies on binding of calcium ions by poly({alpha}-L-guluronate) chains were carried out. Black-Right-Pointing-Pointer The Gibbs free energy landscapes corresponding to the process of calcium binding were calculated. Black-Right-Pointing-Pointer The Effective coordination number parameter was introduced in order to describe the dynamic changes in the arrangement of water molecules coordinating calcium ions. - Abstract: The theoretical studies on binding of calcium ions by poly({alpha}-L-guluronate) chains were carried out to provide the insight into the molecular basis of this process. The three local minima of the Gibbs free energy (corresponding to the two distinct stable states and to the one short living, meta-stable state) were distinguished. The results emphasize the important role of water molecules. The ECN (effective coordination number) parameter was introduced in order to describe the dynamic changes in the arrangement of solvent molecules coordinating calcium ion.

  17. 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.

  18. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma.

    Science.gov (United States)

    Janik, John E; Morris, John C; O'Mahony, Deirdre; Pittaluga, Stefania; Jaffe, Elaine S; Redon, Christophe E; Bonner, William M; Brechbiel, Martin W; Paik, Chang H; Whatley, Millie; Chen, Clara; Lee, Jae-Ho; Fleisher, Thomas A; Brown, Maggie; White, Jeffrey D; Stewart, Donn M; Fioravanti, Suzanne; Lee, Cathryn C; Goldman, Carolyn K; Bryant, Bonita R; Junghans, Richard P; Carrasquillo, Jorge A; Worthy, Tat'Yana; Corcoran, Erin; Conlon, Kevin C; Waldmann, Thomas A

    2015-10-20

    Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody (90)Y-daclizumab. (90)Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with (90)Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25(-) provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated (90)Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients.

  19. Isolation and identification of CD4+CD25+ regulatory T cells in rat

    Institute of Scientific and Technical Information of China (English)

    Ling Lü; Feng Zhang; Liyong Pu; Chao Jiang

    2006-01-01

    Objective: To establish a stable and high efficient method for collection of CD4+CD25+ regulatory T cells from rats in vitro. Methods: CD4+CD25+ regulatory T cells were isolated from the rat splenic cells through two steps by magic cell sorting (MACS) system. The first step was negative selection of CD4+ T cells by cocktail antibodies and anti-IgG magic microbeads, and the second step was positive selection of CD25+ T cells by anti-CD25 PE and anti-PE magic microbeads. The purity and viability of separated cells were measured by flow cytometry (FACS) and Trypan blue staining. The suppressive ability of seperated cells on the proliferation of CD4+CD25- T cells was assessed by cell proliferation assay. Results: The purity of negatively enriched CD4+ T cells was 79%-87% (83.6% ± 2.5%) , and the purity of positively enriched CD4+CD25+ T cells was 86%-93% ( 90.2 ± 1.8%) with the viability of 92%-95% (92.8% ± 3.4%). The enriched cells significantly suppressed the proliferation of CD4+CD25- T cells in mixed lymphocyte culture (P < 0.05). Conclusion: An effective method can be established for enrichment of CD4+CD25+ regulatory T cells in two steps by MACS, with satisfied cell purity, viability and function.

  20. 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.

  1. Genetic recombination within the human T-cell receptor. cap alpha. -chain gene complex

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, M.A.; Kindt, T.J.

    1987-12-01

    Genetic analyses of the human T-cell receptor (TCR) ..cap alpha..-chain genes indicate that recombination events may occur frequently within this gene complex. Examination of the inheritance of restriction fragment length polymorphisms (RFLP) detected by using probes for constant or variable region gene segments made it possible to assign TCR..cap alpha.. haplotypes to the 16 parents and 43 offspring of eight families studied. A total of six RFLP, three for the constant region and three for variable region segments, were examined in the present studies. Most enzyme and probe combinations tested revealed no polymorphism and those finally selected for the study showed limited polymorphism in that only two or, in one case, three allelic forms of the gene were seen. In spite of limited variability at this level, extensive heterogeneity was observed for the combinations of markers present in haplotypes, suggesting that frequent recombination events have occurred. Most strikingly, multiple combinations of RFLP occurring in close proximity of the TCR..cap alpha.. constant region gene were observed in this study. A high recombination frequency for the TCR..cap alpha.. gene complex is further supported by the observation that two children, one in each of two families, inherited recombinant TCR..cap alpha.. haplotypes.

  2. 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.

  3. 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.

  4. 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

  5. CD4+CD25high Regulatory Cells in Peripheral Blood of NSCLC Patients

    Institute of Scientific and Technical Information of China (English)

    LIU Li; YAO Junxia; DING Qian; HUANG Shiang

    2006-01-01

    The proportion and changes of CD4+CD25high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral blood was collected from 61 patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with the flow cytometry for lymphocyte subsets (CD3+, CD4+ and CD8+) and CD4+CD25high Tr cells. The results showed that the proportion of CD4+CD25high Tr cells in NSCLC group was significantly higher than in control group [(4.36±2.07) % vs (2.04±1.03) %, P<0.01]. The proportion of CD4+CD25 high Tr cells in late stage was higher than that in early stage [stages Ⅰ + Ⅱ (2.26±0.6) %; stage Ⅲ (3.28±1.38) %; stage Ⅳ(6.06±4.08) %] (P<0.05). Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher proportion of CD4+CD25high Tr cells in peripheral blood was worse (P=0.0026). In conclusion, the relative increase in CD4+CD25high Tr cells in peripheral blood may be related to immunosuppression and tumor progression in patients with NSCLC. This finding suggests that CD4+CD25+high Tr cells in peripheral blood of NSCLC may be positive for prognosis analysis. The use of depletion of the CD4+CD25high Tr cell therapy to treat NSCLC patients may be an effective strategy.

  6. The IL-15R alpha chain signals through association with Syk in human B cells.

    Science.gov (United States)

    Bulanova, E; Budagian, V; Pohl, T; Krause, H; Dürkop, H; Paus, R; Bulfone-Paus, S

    2001-12-01

    The alpha-chain of the IL-15R (IL-15Ralpha) serves as the specific, high-affinity receptor for IL-15. It is expressed by lymphoid and nonlymphoid cells, including B cell lymphoma lines. In this study, we have further explored IL-15Ralpha-mediated signaling in activated primary B cells and in Raji cells, a human B-lymphoblastoid cell line which expresses the IL-15Ralpha and IL-2Rgamma chains, but lacks the IL-2Rbeta chain. Stimulation of Raji cells with IL-15 induces their proliferation and rescues them from C2-ceramide-induced apoptosis. By immunoprecipitation and Western blotting, we show that treatment of Raji cells and activated primary B cells with IL-15 induces coprecipitation of Syk kinase with the IL-15Ralpha chain. Upon association, the activated Syk kinase phosphorylates the IL-15Ralpha chain as well as phospholipase Cgamma, which coprecipitates with Syk. Furthermore, transfection of Raji cells with stem-loop Syk antisense oligonucleotides prevents IL-15Ralpha and phospholipase Cgamma phosphorylation as well as the inhibition of apoptosis by IL-15. Mutation of a defined region of the intracellular signaling portion of IL-15Ralpha (Tyr227) abrogates both the IL-15Ralpha/Syk association and IL-15Ralpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Ralpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells.

  7. 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

  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. 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.

  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. $^{110,116}$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...

  12. Presence of a polyadenylated RNA fragment encoding the membrane domain for immunoglobulin alpha chain indicates that mRNAs for both secreted and membrane-bound alpha chains can be produced from the same RNA transcript.

    OpenAIRE

    Stavnezer, J.

    1986-01-01

    RNA blotting was employed to examine polyadenylated immunoglobulin alpha chain RNAs in a B lymphoma synthesizing membrane-bound and secretory IgA and in a hybridoma which synthesizes predominantly secretory IgA. Both cell lines were derived from the I.29 lymphoma and expressed the identical heavy chain variable region gene. In addition to the predicted mRNA precursors, four novel species of polyadenylated alpha RNAs were detected. The presence of a RNA species which was too large to have the ...

  13. Quantitative and selective polymerase chain reaction analysis of highly similar human alpha-class glutathione transferases.

    Science.gov (United States)

    Larsson, Emilia; Mannervik, Bengt; Raffalli-Mathieu, Françoise

    2011-05-01

    Alpha-class glutathione transferases (GSTs) found expressed in human tissues constitute a family of four homologous enzymes with contrasting enzyme activities. In particular, GST A3-3 has been shown to contribute to the biosynthesis of steroid hormones in human cells and is selectively expressed in steroidogenic tissues. The more ubiquitous GST A1-1, GST A2-2, and GST A4-4 appear to be primarily involved in detoxification processes and are expressed at higher levels than GST A3-3. We are interested in studying the cell and tissue expression of the GST A3-3 gene, yet the existence of highly expressed sequence-similar homologs and of several splice variants is a serious challenge for the specific detection of unique transcript species. We found that published polymerase chain reaction (PCR) primers for GST A3-3 lack the specificity required for reliable quantitative analysis. Therefore, we designed quantitative PCR (qPCR) primers with greatly increased discrimination power for the human GSTA3 full-length transcript. The improved primers allow accurate discrimination between GST A3-3 and the other alpha-class GSTs and so are of great value to studies of the expression of the GSTA3 gene. The novel primers were used to quantify GSTA3 transcripts in human embryonic liver and steroidogenic cell lines.

  14. Lenalidomide potentiates CD4(+)CD25(+)Treg-related suppression of lymphoma B-cell proliferation.

    Science.gov (United States)

    Grygorowicz, Monika Anna; Borycka, Ilona Sara; Nowak, Eliza; Paszkiewicz-Kozik, Ewa; Rymkiewicz, Grzegorz; Błachnio, Katarzyna; Biernacka, Marzena; Bujko, Mateusz; Walewski, Jan; Markowicz, Sergiusz

    2016-03-10

    We have previously found that ex vivo expanded human CD4(+)CD25(+)Treg cells suppress proliferation of lymphoma B-cell lines. Here we demonstrate that the immunomodulatory drug lenalidomide potentiates suppression of lymphoma B-cell proliferation by freshly isolated CD4(+)CD25(+)Tregs, as well as suppression by Tregs expanded polyclonally in the presence of rapamycin from CD4(+)CD25(+)T cells or CD4(+)CD25(+)CD127(lo)T cells. The regulation of lymphoma cell proliferation by Tregs pre-expanded with "third-party" allogeneic MoDCs in the presence of rapamycin was also potentiated by lenalidomide. Lenalidomide contributed to the suppression exerted by Tregs despite concomitant downregulation of Treg proliferation. Lenalidomide did not reduce the suppression of conventional T cells by expanded Tregs. The exposure of polyclonally expanded Tregs to lenalidomide did not significantly alter their phenotype. There was no uniform pattern of lenalidomide effect on Treg-mediated regulation of lymphoma B cells freshly isolated from patients. Freshly isolated lymphoma cells activated with multimeric CD40L and IL-4 to support their survival in vitro varied in their sensitivity to lenalidomide, and the regulatory effect of Tregs on such lymphoma cells ranged from suppression to help in individual patients. Lenalidomide potentiated or attenuated Treg effects on the survival of freshly isolated lymphoma cells. A combination of lenalidomide treatment with adoptive transfer of CD4(+)CD25(+)Tregs or CD4(+)CD25(+)CD127(lo)Tregs expanded ex vivo could be used to suppress proliferation of residual lymphoma in select patients with lymphoma responsive to the regulation by Tregs and sensitive to lenalidomide.

  15. Functional and Developmental Analysis of CD4+CD25+ Regulatory T Cells under the Influence of Streptococcal M Protein in Rheumatic Heart Disease

    Directory of Open Access Journals (Sweden)

    Nidhal Abdul-Auhaimen

    2011-06-01

    Full Text Available The purpose of this study was to determine the role of streptococcal M protein in naturally-occurring CD4+CD25+ regulatory T cells (nTregs function and development in rheumatic heart disease in Iraqi patients. Streptococcus pyogenes was isolated for subsequent M protein extraction. Also, peripheral blood nTregs and CD4+ T cells were isolated by using Magnetic Cell Separation System. Tissue culture for isolated cells was performed in the presence and absence of M protein. Cell count was performed, and tumor necrosis factor alpha (TNF-α and interleukin-4 (IL-4 were determined in culture supernatant using ELISA system. There was a significant positive correlation (P0.05, association (r=0.353 between the mean number of nTregs and CD4+ T cells in the presence of M protein. The M protein stimulated CD4+ T cells to produce IL-4 in very little amount (<4 pg/ml in all samples. Compared to the production of IL4, TNF-α was produced in higher concentrations in the culture supernatants. The findings of the study indicate that streptococcal M protein has an important role in increasing the proliferation of CD4+CD25+regulatory T cells and CD4+ T cells. However, CD4+CD25+ regulatory T cells have lower suppressive activity against CD4+ T cells in the presence of M protein

  16. Functional and Developmental Analysis of CD4+CD25+ Regulatory T Cells under the Influence of Streptococcal M Protein in Rheumatic Heart Disease

    Science.gov (United States)

    Abdul-Auhaimena, Nidhal; Al-Kaabi, Zaman I. L

    2011-01-01

    The purpose of this study was to determine the role of streptococcal M protein in naturally-occurring CD4+CD25+ regulatory T cells (nTregs) function and development in rheumatic heart disease in Iraqi patients. Streptococcus pyogenes was isolated for subsequent M protein extraction. Also, peripheral blood nTregs and CD4+ T cells were isolated by using Magnetic Cell Separation System. Tissue culture for isolated cells was performed in the presence and absence of M protein. Cell count was performed, and tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4) were determined in culture supernatant using ELISA system. There was a significant positive correlation (P0.05), association (r=0.353) between the mean number of nTregs and CD4+ T cells in the presence of M protein. The M protein stimulated CD4+ T cells to produce IL-4 in very little amount (<4 pg/ml) in all samples. Compared to the production of IL4, TNF-α was produced in higher concentrations in the culture supernatants. The findings of the study indicate that streptococcal M protein has an important role in increasing the proliferation of D4+CD25+regulatory T cells and CD4+ T cells. However, CD4+CD25+ regulatory T cells have lower suppressive activity against CD4+ T cells in the presence of M protein. PMID:23359747

  17. 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.

  18. 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).

  19. Identification of a cell lineage-specific gene coding for a sea urchin alpha 2(IV)-like collagen chain.

    Science.gov (United States)

    Exposito, J Y; Suzuki, H; Geourjon, C; Garrone, R; Solursh, M; Ramirez, F

    1994-05-06

    We report the isolation of several overlapping cDNAs from an embryonic library of Strongylocentrotus purpuratus coding for a novel sea urchin collagen chain. The conceptual amino acid translation of the cDNAs indicated that the protein displays the structural features of a vertebrate type IV-like collagen alpha chain. In addition to a putative 31-residue signal peptide, the sea urchin molecule contains a 14-residue amino-terminal non-collagenous segment, a discontinuous 1,477-amino acid triple helical domain, and a 225-residue carboxyl-terminal domain rich in cysteines. The amino- and carboxyl-terminal non-collagenous regions of the echinoid molecule are remarkably similar to the 7 S and carboxyl-terminal non-collagenous (NC1) domains of the alpha 1 and alpha 2 chains of vertebrate type IV collagen. The sequence similarity and distinct structural features of the 7 S and NC1 domains strongly suggest that the sea urchin polypeptide is evolutionarily related to the alpha 2(IV) class of collagen chains. Finally, in situ hybridizations revealed that expression of this collagen gene is restricted to the mesenchyme cell lineage of the developing sea urchin embryo.

  20. Detection of CD4+CD25+ T cells in peripheral blood of patients with aplastic anemia%再生障碍性贫血患者外周血CD4+CD25+ T细胞的检测

    Institute of Scientific and Technical Information of China (English)

    王卫国; 马黎丽; 马芳; 李玉云

    2012-01-01

    Objective: To explore the relationship between the level of CD4 + CD25 + T cells and pathogenesis or prognosis of aplastic anemia by detecting CD4 + CD25 + T cells in peripheral blood. Methods: The proportion of CD4 + CD25 + T cells and CD4 + CD25high T cells in peripheral blood of four groups, including 20 cases of healthy individuals as normal controls ,30 cases of patients with first onset of aplastic anemia, 10 cases of patients accepted effective treatment and 10 cases of patients accepted invalid treatment, were determined by flow cytometry. Results: The rate of CD4 + CD25 + T cells in peripheral blood of four groups was not significantly different ( P > 0.05) ; Compared with group of normal controls, the rate of CD4+ CD25high T cells in patients with first onset of aplastic anemia decreased significantly ( P 0. 05 ). Conclusions: The decreasing of CD4 + CD25highT cells is one of the reasons causing breakdown of immune tolerance in patients with aplastic anemia,the rate of CD4 CD25 T cells may not reflect the prognosis of the patients.%目的:通过对外周血CD4+CD25+T细胞的检测,初步探讨CD4+CD25+T细胞水平与再生障碍性贫血(aplastic anemia,AA)发病和预后的关系.方法:流式细胞术分别检测20例正常对照、30例初发AA患者、10例治疗有效AA患者和10例治疗无效AA患者的CD4+CD25+T细胞和CD4+CD25highT细胞水平.结果:4组患者CD4+CD25+T细胞比例差异无统计学意义(P>0.05);初发AA和治疗无效组AA患者CD4+CD25highT细胞比例均低于正常对照组(P0.05).结论:CD4+CD25highT细胞比例下降是造成AA患者免疫耐受破坏的原因之一,CD4+CD25+T细胞比例可能并不能反映AA患者的预后状况.

  1. 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.

  2. 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.

  3. Identification of lesional CD4+ CD25+ Foxp3+ regulatory T cells in Psoriasis.

    NARCIS (Netherlands)

    Bovenschen, H.J.; Vlijmen-Willems, I.M.J.J. van; Kerkhof, P.C.M. van de; Erp, P.E.J. van

    2006-01-01

    BACKGROUND: Depletion of CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (T(reg)) induces autoimmune phenomena. These cells have not yet been fully characterized in the skin of psoriatic patients. OBJECTIVES: To prove that the Zenon immunofluorescent labeling technique is suitable for the d

  4. 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.

  5. 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...... investigated the expression of FoxP3 and regulatory potential of gut-derived CD4(+)CD25(+) T cells cultured from patients with CD and healthy individuals. The FoxP3 expression was analysed by reverse transcriptase polymerase chain reaction (RT-PCR), and the suppressive effect of FoxP3(+)CD4(+)CD25(+) T cells...... on proliferation and cytokine production of autologous CD4(+) T cells was assessed by flow cytometry. Cultured gut-derived T cells with CD4(+)CD25(+) phenotype expressed FoxP3 and were able as the freshly isolated T(regs) from peripheral blood to suppress proliferation and cytokine production of autologous CD4...

  6. Influence of CD4+CD25+ T cells on Plasmodium berghei NK65 infection in BALB/c mice.

    Science.gov (United States)

    Long, Ton That Ai; Nakazawa, Shusuke; Onizuka, Shozaburo; Huaman, Maria Cecilia; Kanbara, Hiroji

    2003-02-01

    CD4(+) T cells co-expressing CD25 (CD4(+)CD25(+) T cells) have been identified as immunoregulatory suppressors modulating autoimmune response. Beside that, autoimmune response was supposed to be associated with malaria infection. Based on these data, we hypothesised that CD4(+)CD25(+) T cells may influence protective immunity to malaria parasites, while suppressing autoimmune response arising throughout the course of malarial infection. To test this possibility, we evaluated the kinetics of CD4(+)CD25(+) T cells during malaria infection and investigated the influence of CD25 depletion by anti-mouse CD25 monoclonal antibody (PC61) on the infection, using a mouse model of premunition to Plasmodium berghei NK65 malaria. The results showed that, during exacerbation of P. berghei NK65 infection, the proportion of CD4(+)CD25(+) T cells among CD4(+) T cells decreased, although that of CD4(+) T cells increased. CD25 depletion clearly delayed the growth of parasitaemia during parasite challenge, particularly in immunised mice. These findings demonstrated that CD4(+)CD25(+) T cells are able to influence protective immunity underlying premunition to P. berghei NK65 parasites.

  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. 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.

  9. 阻断ICOS/B7h信号的供体特异性输血对移植受体CD4+CD25+调节性T细胞的影响%Influence of donor specific transfusion with impaired ICOS/B7h allorecognition on CD4 + CD25+regulatory T cells of cardiac allograft recipient

    Institute of Scientific and Technical Information of China (English)

    杜峻峰; 李世拥; 于波; 白雪; 左富义

    2010-01-01

    transplanted in the neck of C57BL/6, without treatment. In treatment group, a combination of 5 × 106 ICOS-Fcrecipient C57BL/6 mice following a heterotopic cardiac allograft transplantation. Graft function was assessed daily by palpation, with rejection defined as the absence of detectable beating, then survival of grafts was recorded. CD4 + CD25 + Treg subsets in the peripheral blood of allograft recipients were analyzed by flow cytometry. The expression of FOXP3 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). To assess the suppressive activity of CD4 + CD25 + Treg from tolerant C57BL/6 mice on CD4 + CD25- Teff from naive BALB/C mice, suppression allogeneic MLR assays were performed in vitro.Results In comparison with allogenic group, the survival of cardiac grafts could be prolonged by the comICOS-Fc on the day 0-6 [(84.38 ± 29. 14) days vs (7.00 ± 0. 76) days, P < 0. 01]. Among 3 groups, a considerable proportion of CD4 + CD25 + Treg could be observed in treatment group [(15.60 ± 5.69 )% ,P <0. 01], meanwhile, high expression of FOXP3 mRNA was also detected within allografts in treatment group.Furthermore, in contrast to naive C57BL/6 mice, CD4+ CD25 + Treg harvested from tolerant C57BL/6 mice showed more potent suppressive effect on the proliferation of CD4 + CD25 - Teff. Conclusion Allograft tolerance can be induced by donor specific transfusion with impaired ICOS/B7h allorecognition. CD4 + CD25 + Treg played a critical role in the establishment and the maintenance of this allograft tolerance.

  10. Separation and characterization of alpha-chain subunits from tilapia (Tilapia zillii) skin gelatin using ultrafiltration.

    Science.gov (United States)

    Chen, Shulin; Tang, Lanlan; Su, Wenjin; Weng, Wuyin; Osako, Kazufumi; Tanaka, Munehiko

    2015-12-01

    Alpha-chain subunits were separated from tilapia skin gelatin using ultrafiltration, and the physicochemical properties of obtained subunits were investigated. As a result, α1-subunit and α2-subunit could be successfully separated by 100 kDa MWCO regenerated cellulose membranes and 150 kDa MWCO polyethersulfone membranes, respectively. Glycine was the most dominant amino acid in both α1-subunit and α2-subunit. However, the tyrosine content was higher in α2-subunit than in α1-subunit, resulting in strong absorption near 280 nm observed in the UV absorption spectrum. Based on the DSC analysis, it was found that the glass transition temperatures of gelatin, α1-subunit and α2-subunit were 136.48 °C, 126.77 °C and 119.43 °C, respectively. Moreover, the reduced viscosity and denaturation temperature of α1-subunit were higher than those of α2-subunit, and the reduced viscosity reached the highest when α-subunits were mixed with α1/α2 ratio of approximately 2, suggesting that α1-subunit plays a more important role in the thermostability of gelatin than α2-subunit.

  11. Alpha decay chains study for the recently observed superheavy element Z=117 within the Isospin Cluster Model

    CERN Document Server

    Kumar, Sushil

    2011-01-01

    The recently observed $\\alpha$-decay chains $^{293-294}117$ were produced by the fusion reactions with target $^{249}Bk$ and projectile $^{48}Ca$ at Dubna in Russia. The reported cross-sections for the mentioned reaction are $\\sigma=0.5(+1.1,-0.4)$pb and $\\sigma$=1.3(+1.5,-0.6)$pb$ at $E^{*}=35MeV$ and $E^{*}=39MeV$, respectively. The Q-values of $\\alpha$-decay and the half-lives $Log_{10}T^{\\alpha}_{1/2}$(s) are calculated for the $\\alpha$-decay chains of $^{293-294}117$ nuclei, within the framework of Isospin Cluster Model (ICM). In the ICM model the proximity energy is improved by using the isospin dependent radius of parent, daughter and alpha particle. The binding energy $B(A_{i}, Z_{i})$ (i=1,2) of any nucleus of mass number A and atomic number Z was obtained from a phenomenological and more genaralized BW formula given by \\cite{samanta02}. The calculated results in ICM are compared with the experimental results and other theoretical Macro-Microscopic(M-M), RMF(with NL3 and SFU Gold forces parameter) mo...

  12. 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

  13. Armor: An {alpha}{beta}{gamma} assembly for irradiated fuel analysis; Armor: Chaine {alpha}{beta}{gamma} pour l'analyse des combustibles irradies

    Energy Technology Data Exchange (ETDEWEB)

    Beraud, M. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1967-04-15

    The assembly ARMOR which was built with a view to carrying out research on irradiated fuels consists of an {alpha}{beta}{gamma} enclosure made up of 11 cells in line. After a general description of the assembly in its present form, the various functions are reviewed: introduction of the samples, chemical de-canning, dissolution of the irradiated uranium pellets, preparation of solutions for mass spectrometric analyses, disposal of the effluents and of the solid waste. The assembly-has been working since 1961. During the 5 to 6 years operation, various improvements have been made and a certain number of observations have been collected concerning the work. (author) [French] Construite en vue de repondre a un programme d'etudes de combustibles Irradies, la chaine Armor est une enceinte {alpha}{beta}{gamma} composee de 11 cellules en ligne. Apres une description generale de la chaine dans son etat actuel, les differentes fonctions sont passees en revue: entree des echantillons, degainage chimique, dissolution des pastilles d'uranium irradie, preparation des solutions pour les analyses par spectrometrie de masse, rejet des effluents et des dechets solides. La chaine est en service depuis 1961. Au cours des cinq a six annees d'exploitation, differentes ameliorations ont ete apportees et un ensemble d'observations sur le travail a ete recueilli. (auteur)

  14. CD4(+)CD25(+)Tregs express an increased LAG-3 and CTLA-4 in anterior chamber-associated immune deviation

    NARCIS (Netherlands)

    Zhu, X.F.; Yang, P.Z.; Zhou, H.Y.; Li, B.; Huang, X.K.; Meng, Q.L.; Wang, L.; Kijlstra, A.

    2007-01-01

    Background Regulatory CD4+CD25+ T cells have been proven to be essential for maintenance of peripheral tolerance and autoimmune diseases. ACAID is a model of immune privilege in the eye. Relatively little is known about the role and phenotype of these regulatory CD4+CD25+ T cells in ACAID. Methods I

  15. Effect of dendritic cells on the generation of CD4+CD25+Foxp3+ T cells.

    OpenAIRE

    Ivo Marguti

    2007-01-01

    As células dendríticas (DCs) são as principais células apresentadoras de antígeno do sistema imune. No entanto, trabalhos têm demonstrado seu envolvimento na manutenção da tolerância imunológica. As células T CD4+CD25+Foxp3+ possuem a capacidade de suprimir respostas imunes. Neste estudo avaliamos as alterações ocorridas na população de células T CD4+CD25+Foxp3+ após co-cultura de células de linfonodo com DCs. Nossos resultados demonstram que após a co-cultura há um aumento da população de cé...

  16. 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

    -specific probes confirmed the inheritance of the mutation with the phenotype. The mutation changed the GGC codon for glycine-1143 to GAC for aspartate. Substitution of glycine-1143, located in the collagenous domain of the alpha 5(IV) chain, for any other amino acid can be expected to interfere......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...... gradient gel electrophoresis analysis suggested a sequence variant in the proband and his mother. This was confirmed by sequencing of the PCR-amplified exon 14 region of the hemizygous proband, which demonstrated the base change G----A abolishing an MspI restriction site. Hybridization analysis with allele...

  17. 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

  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. 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.

  20. Assembly, intracellular processing, and expression at the cell surface of the human alpha beta T cell receptor/CD3 complex. Function of the CD3-zeta chain

    DEFF Research Database (Denmark)

    Geisler, C; Kuhlmann, J; Rubin, B

    1989-01-01

    The TCR/CD3 complex is a multimeric protein complex composed of a minimum of seven transmembrane chains (TCR alpha beta-CD3 gamma delta epsilon zeta 2). Whereas earlier studies have demonstrated that both the TCR-alpha and -beta chains are required for the cell surface expression of the TCR/CD3 c...... to form the heptameric complex (TCR alpha beta-CD3 gamma delta epsilon----TCR alpha beta-CD3 gamma delta epsilon 2); and 5) CD3-zeta is required for the export of the TCR/CD3 complex from the endoplasmic reticulum to the Golgi apparatus for subsequent processing....

  1. 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.

  2. 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 placenta...

  3. CD4+CD25+T细胞的扩增方法与临床应用%The proliferation and clinical application of CD4+ CD25+ regulatory T-cell

    Institute of Scientific and Technical Information of China (English)

    王慧

    2008-01-01

    CD4+CD25+T细胞是最重要的一类调节性T细胞(Tr).体内固有CD4+CD25+T细胞的自然扩增率极低,不能满足临床治疗的需要.通过采用FoxP3基因转染技术、阻断细胞活化信号、DC诱导、加入细胞因子等方法,对CD4+CD25+T细胞的数量和功能进行扩增,使其在器官移植、自身免疫性疾病和肿瘤免疫等领域具有广泛的临床应用前景.%CD4+ CD25+ T cells are the most important cells among the regulatory T-cells. It is known that thenatural proliferation of natural-occurring CD4+ CD25+ Tcell is very low, and is not satisfied for the clinical ther-apies. However, the quantity and function of CD4+ CD25+ T could be increased through FoxP3 gene transfec-tion, activation signal blockade, dendritil cell induction, and cytokine stimulation. Thus the clinical applicationof CD4+ CD25+ T in organ transplantation, autoimmune disease and tumor immunity areas will be possitble.

  4. 免疫磁珠两步法分离小鼠脾脏CD4+CD25+调节性T细胞%Concentration of Mouse Splenic CD4+CD25+ Regulatory T Cell by Magnetic Cell Sorting System

    Institute of Scientific and Technical Information of China (English)

    印永祥; 韩晓枫; 何阳

    2009-01-01

    体外分离CD4+CD25+调节性T细胞(CD4+CD25+Treg)并进行初步鉴定.用磁性细胞分离器(MiniMACS)分离CD4+CD25+Treg细胞,流式细胞术(flow cytometry,FCM)分析细胞纯度和Foxp3蛋白表达,体外检测细胞因子.MACS分离的CD4+CD25+Treg细胞纯度大于90%,细胞存活率大于93%,并且特异性表达Foxp3蛋白,体外能抑制CD4+CD25-Treg分泌IFN-γ,同时CD4+CD25+Treg能分泌抑制性细胞因子TGF-β1、IL-10.结果显示,通过MACS可分离高纯度、高活性的CD4+CD25+Treg细胞.

  5. In vitro inhibition of enterobacteria-reactive CD4+CD25- T cells and suppression of immunoinflammatory colitis in mice by the novel immunomodulatory agent VGX-1027

    DEFF Research Database (Denmark)

    Mangano, Katia; Sardesai, Niranjan; D'Alcamo, Maria;

    2008-01-01

    VGX-1027 is an isozaxoline compound that has recently been found to primarily target the function of murine macrophages but not of T cells, inhibiting secretion of tumor necrosis factor (TNF)-alpha in response to different Toll-like receptor agonists in vitro and in vivo. The well-defined role...... inflammatory colitis induced in mice by intracolonic challenge with dinitrobenzene sulfonic acid. The data from the two sets of experiments revealed that VGX-1027 inhibited both proliferation of enterobacterial antigen-reactive CD4+CD25- T cells in vitro and the development of clinical and histological signs...... of colitis in vivo. The beneficial effect in this model was associated with reduced colonic production of proinflammatory cytokines such as interleukin (IL)-1beta, TNF-alpha, IL-12p70 and interferon (IFN)-gamma and lower content of nuclear factor (NF)-kappaB (p65). These findings seem to warrant...

  6. 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

  7. Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue.

    Science.gov (United States)

    Polak, Jan; Moro, Cédric; Bessière, David; Hejnova, Jindra; Marquès, Marie A; Bajzova, Magda; Lafontan, Max; Crampes, Francois; Berlan, Michel; Stich, Vladimir

    2007-10-01

    The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.

  8. The change of CD4+ CD25+ Treg cells in the collagen-induced arthritis mouse model transplanted with mesenchymal stem cells%骨髓间充质干细胞对胶原诱导的关节炎大鼠CD4+CD25+调节性T细胞的影响

    Institute of Scientific and Technical Information of China (English)

    张明生; 穆永慧; 陈清汉; 朱宇

    2014-01-01

    Objective To observe the immunologic effect of transplantation of mesenchymal stem cells (MSCs) on CD4+ CD25 + Treg cells frequency and function in collagen-induced arthritis (CIA) rat model.Methods Rat CIA model was established by immunizing SD rats with type Ⅱ collagen.MSCs were purified and cultured from the bone marrow of SD rats,then transplanted to CIA model.The frequency of CD4 + CD25 + Treg cells in the spleen was measured by flow cytometry (FCM) respectively after the MSCs transplantation,and the expression of forkhead box P3 (Foxp3),transforming growth factor-β1 (TGF-β1)and interleukin (IL)-10 mRNA was evaluated by real-time quantitative polymerase chain reaction (Real-time PCR).CD4 + CD25 + Treg cells were isolated from the spleen of rats by immunomagnetic beads and the inhibitory effect of CD4 + CD25 + Treg cells on proliferation of CD4 + CD25-Teff cells was estimated by methyl thiazol tetrazolium (MTT) colorimetry.Results The MSCs transplantation relieved the arthritis symptom of the CIA rats.The frequency of CD4 + CD25 + Treg cells in the spleen of MSCs-treated CIA rats was increased significantly (P < 0.05) as compared with the CIA group,and the levels of Foxp3,IL-10 and TGF-β1 mRNA were also significantly increased (P < 0.05).CD4 + CD25 + Treg cells isolated from treatment group showed higher inhibition on the proliferation of CD4 + CD25-Teff cells versus CD4 + CD25 +Treg cells isolated from CIA rats.Conclusion Transplantation of MSCs is effective on preventing the de-velopment of CIA.The increased frequency and reinforced function of CD4+ CD25 + Treg cells may be one of the mechanisms for MCSs transplantation treating CIA in rats.%目的 观察间充质干细胞(MSCs)对Ⅱ型胶原诱导的关节炎(CIA)大鼠Treg细胞数量和功能的影响.方法 以Ⅱ型胶原蛋白免疫SD大鼠建立CIA动物模型;分离培养正常SD大鼠骨髓MSCs,尾静脉移注CIA大鼠;流式细胞仪检测大鼠脾脏CD4 +CD25+T细胞比例变化;实时

  9. 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.

  10. Branched chain amino acid transaminase and branched chain alpha-ketoacid dehydrogenase activity in the brain, liver and skele­tal muscle of acute hepatic failure rats

    Directory of Open Access Journals (Sweden)

    Takei,Nobuyuki

    1985-02-01

    Full Text Available Branched chain amino acid (BCAA transaminase activity increased in both the mitochondrial and supernatant fractions of brain from hepatic failure rats, in which a partial hepatectomy was performed 24h following carbon tetrachloride (CCl4 administration, although the activity of liver and skeletal muscle was the same as in control rats. The elevation of mitochondrial BCAA transaminase activity in liver-injured rats was partly due to increased activity of brain specific Type III isozyme. Branched chain alpha-ketoacid (BCKA dehydrogenase in the brain homogenates was not significantly altered in acute hepatic failure rats, while the liver enzyme activity was markedly diminished. BCKA dehydrogenase activity in the brain homogenates was inhibited by adding ATP to the assay system, and was activated in vitro by preincubating the brain homogenate at 37 degrees C for 15 min. These findings suggest that brain BCAA catabolism is accelerated in acute hepatic failure rats.

  11. [In vitro amplification of CD4(+) CD25(+) regulatory T cells and identification of amplified T cell immunosuppressive function].

    Science.gov (United States)

    Weng, Wen-Jun; Pan, Li; Fang, Jian-Pei; Xu, Lv-Hong

    2013-10-01

    This study was purposed to compare the effect of 3 different cell components for expanding CD4(+) CD25(+) Treg in vitro, and identify their immunosuppressive function. CD4(+) T cells, CD4(+) CD25(-)T cells and CD4(+) CD25(+)T cells were isolated from mouse splenocytes by MACS and then expanded in vitro. Phenotype of the T cell lines and expression of the FOXP3 was determined by flow cytometry. The inhibitory effect of expanded CD4(+) CD25(+) T cells on CD4(+) CD25(-)T cells was tested by MLR method. The results showed that the Treg cells from all the three groups were expanded significantly after culture for 2 weeks. In the CD4(+) T cells group, the proliferation rate was (77.8 ± 5.32) folds with a percentage of Treg cells increasing from (6.61 ± 1.00)% to (15.33 ± 1.31)%. The proliferation rate in the CD4(+) CD25(-) T cells group was (95.20 ± 7.67) folds, with the percentage of CD4(+) CD25(+) T cells raising from (0.37 ± 0.13)% to (9.84 ± 0.98)%. The proliferation rate in the CD4(+) CD25(+) T cells group was (41.20 ± 6.92) folds, the proportion of Treg cells decreased from (86.75 ± 1.25)% to (85.32 ± 1.62)%, and the expression of Foxp3 decreased from (76.92 ± 1.72)% to (75.33 ± 2.11)% during the culture, there were not significant differences in the cell purity and the expression of Foxp3, compared with pre-amplification. The inhibitory test showed that the expanded CD4(+) CD25(+) T cells could inhibit the proliferation of CD4(+) CD25(-) T cells in vitro in a cell dose-dependent manner. It is concluded that the amplification of CD4(+) CD25(+) Treg cells is successful in vitro, especially in the CD4(+) CD25(+) T cells group, the cell purity and Foxp3 gene is not obviously changes after amplification.

  12. Do CD4+CD25+ Immunoregulatory T Cells Hinder Tumor Immunotherapy?

    OpenAIRE

    Antony, Paul Andrew; Restifo, Nicholas P.

    2002-01-01

    After years of banishment from mainstream immunology, the notion that one subset of T cells can exert regulatory effects on other T lymphocytes is back in fashion. Recent work in knockout and transgenic mice has begun to bring molecular definition to our understanding of immunoregulatory CD4+CD25+ T cells (Treg/Th3/Tr1). The identification of the glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18) expressed on T regulatory cells might affor...

  13. Detection of CD4 + CD25 + Tree Cells and Foxp3 in Pathogenesis of Preeclampsia%子痫前期发病中CD4+CD25+Treg细胞与Foxp3的检测及意义

    Institute of Scientific and Technical Information of China (English)

    王莲莲; 曹霞; 魏军

    2011-01-01

    [目的]研究CD4+ CD25+调节性T细胞(CD4+ CD25+Treg细胞)和Foxp3基因表达与子痫前期发病的相关性.[方法]选择住院确诊的妊娠期高血压孕妇12例(A组)、轻度子痫前期(MPE)孕妇14例(B组)、重度子痫前期(SPE)孕妇15例(C组),30例正常妊娠晚期孕妇为对照组(D组),应用流式细胞术检测并比较四组外周血中CD4+ CD25+ Treg和 Foxp3的表达水平.[结果]A组、B组和C组孕妇外周血CD4+ CD25+ Treg 和Foxp3表达水平均显著低于对照组(P<0.05);C组外周血CD4+ CD25+ Treg和Foxp3表达水平显著低于A组和B组(P<0.05).[结论]子痫前期患者体内存在CD4+ CD25+ Treg细胞的异常,CD4+ CD25+Treg细胞的数量的减少和Foxp3表达的降低使CD4+ CD25+Treg细胞免疫抑制功能减弱,从而使母胎免疫耐受失衡,导致子痫前期的发生.%[Objective] To investigate the relationship between CD4+ CD25 + Treg cells, Foxp3 gene ex pression and the pathogenesis of preeclampsia. [Methods] Twelve pregnant women with gestational hyperten sion(group A) , 14 mild preeclampsia(MPE) pregnant women(group B) , 15 severe preeclampsia(SPE) preg nant women(group C) and 30 normal pregnant women(group D) were chosen in hospital. Flow cytometry was used to detect and compare CD4 + CD25 + Treg cells and expression level of Foxp3 in peripheral blood among 4 groups. [Results] The CD4 + CD25 + Treg cells and Foxp3 expression level in peripheral blood in group A, B and C were significantly lower than those in control group( P <0.05). The CD4 + CD25 + Treg cells and Foxp3 expression level in peripheral blood in group C were significantly lower than those in group ∧ and B( P <0.05). [Conclusion] Preeclampsia patients have abnormal CD4 + CD25 + Treg cells. The decrease of CD4 + CD25 +Treg cells and Foxp3 expression attenuates the immune suppression function of CD4 + CD25 + Treg cells, thus maternal-fetal immune tolerance becomes imbalance which results in the occurrence of preeclampsia.

  14. 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.

  15. Association between genetic polymorphisms in the human interleukin-7 receptor alpha-chain and inhalation allergy

    DEFF Research Database (Denmark)

    Shamim, Z; Müller, K; Svejgaard, A;

    2007-01-01

    Thymic stromal-derived lymphopoietin (TSLP) and interleukin-7 share a common receptor chain, IL-7Ralpha. IL-7 is involved in T-cell homeostasis, and TSLP induces production of pro-allergic cytokines. The gene encoding the IL-7Ralpha chain is polymorphic, and investigation of inhalation allergic p...

  16. 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.

  17. 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

  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. Glucosamine Modulates T Cell Differentiation through Down-regulating N-Linked Glycosylation of CD25.

    Science.gov (United States)

    Chien, Ming-Wei; Lin, Ming-Hong; Huang, Shing-Hwa; Fu, Shin-Huei; Hsu, Chao-Yuan; Yen, B Lin-Ju; Chen, Jiann-Torng; Chang, Deh-Ming; Sytwu, Huey-Kang

    2015-12-04

    Glucosamine has immunomodulatory effects on autoimmune diseases. However, the mechanism(s) through which glucosamine modulates different T cell subsets and diseases remain unclear. We demonstrate that glucosamine impedes Th1, Th2, and iTreg but promotes Th17 differentiation through down-regulating N-linked glycosylation of CD25 and subsequently inhibiting its downstream Stat5 signaling in a dose-dependent manner. The effect of glucosamine on T helper cell differentiation was similar to that induced by anti-IL-2 treatment, further supporting an IL-2 signaling-dependent modulation. Interestingly, excess glucose rescued this glucosamine-mediated regulation, suggesting a functional competition between glucose and glucosamine. High-dose glucosamine significantly decreased Glut1 N-glycosylation in Th1-polarized cells. This finding suggests that both down-regulated IL-2 signaling and Glut1-dependent glycolytic metabolism contribute to the inhibition of Th1 differentiation by glucosamine. Finally, glucosamine treatment inhibited Th1 cells in vivo, prolonged the survival of islet grafts in diabetic recipients, and exacerbated the severity of EAE. Taken together, our results indicate that glucosamine interferes with N-glycosylation of CD25, and thereby attenuates IL-2 downstream signaling. These effects suggest that glucosamine may be an important modulator of T cell differentiation and immune homeostasis.

  20. Mechanisms of activation of muscle branched-chain alpha-keto acid dehydrogenase during exercise in man

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; MacLean, D A; Saltin, B

    1996-01-01

    1. Exercise leads to activation (dephosphorylation) of the branched-chain alpha-keto acid dehydrogenase (BCKADH). Here we investigate the effect of low pre-exercise muscle glycogen content and of branched-chain amino acid (BCAA) ingestion on the activity of BCKADH at rest and after 90 min of one......-leg knee-extensor exercise at 65% maximal one-leg power output in five subjects. 2. Pre-exercise BCAA ingestion (308 mg BCAAs (kg body wt)-1) caused an increased muscle BCAA uptake, a higher intramuscular BCAA concentration and activation of BCKADH both at rest (9 +/- 1 versus 25 +/- 5% for the control...... and BCAA test, respectively) and after exercise (27 +/- 4 versus 54 +/- 7%). 3. At rest the percentage active BCKADH was not different, 6 +/- 2% versus 5 +/- 1%, in the normal and low glycogen content leg (392 +/- 21 and 147 +/- 34 mumol glycosyl units (g dry muscle)-1, respectively). The post...

  1. 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.

  2. 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....

  3. Homozygosity for the E526V Mutation in Fibrinogen A Alpha-Chain Amyloidosis: The First Report

    Directory of Open Access Journals (Sweden)

    Isabel Tavares

    2015-01-01

    Full Text Available Systemic hereditary amyloidoses are autosomal dominant diseases associated with mutations in genes encoding ten different proteins. The clinical phenotype has implications on therapeutic approach, but it is commonly variable and largely dependent on the type of mutation. Except for rare cases involving gelsolin or transthyretin, patients are heterozygous for the amyloidogenic variants. Here we describe the first patient identified worldwide as homozygous for a nephropathic amyloidosis, involving the fibrinogen variant associated with the fibrinogen alpha-chain E526V (p.Glu545Val mutation. In 1989, a 44-year-old woman presented with hypertension, hepatosplenomegaly, nephrotic syndrome, and renal failure. She started hemodialysis in 1990 and 6 years later underwent isolated kidney transplantation from a deceased donor. Graft function and clinical status were unremarkable for 16 years, despite progressively increased left ventricular mass on echocardiography. In 2012, 4 months before death, she deteriorated rapidly with severe heart failure, precipitated by Clostridium difficile colitis and urosepsis. Affected family members developed nephropathy, on average, nearly three decades later, which may be explained by the gene dosage effects on the phenotype of E526V (p.Glu545Val fibrinogen A alpha-chain amyloidosis.

  4. 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

    Fetal antigen (FA2) was purified from second trimester human amniotic fluid by immunospecific chromatography, gel filtration and reversed-phase chromatography. Gel filtration revealed two molecular forms of FA2 eluting at volumes corresponding to an M(r) of approximately 100 kDa and 30 kDa. SDS-P...... to that of FA2 in human skin. FA2 is a circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I, and this is the first description of its isolation and structural characterization in humans. Udgivelsesdato: 1992-Dec...... 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...

  5. Isolation, purification and function of mouse CD4 + CD25+ regulatory T lymphocytes in vitro%小鼠CD4+CD25+T调节细胞的分离、纯化及其功能检测

    Institute of Scientific and Technical Information of China (English)

    王百林; 刘增军; 翟淑萍; 陈义发; 秦欢; 刘秋玲

    2010-01-01

    Objective To establish a method for isolation and purification of CD4+ CD25+ regulatory T lymphocytes (Treg), and to identify partial functions of these cells. Methods Lymphocytes were isolated from the mouse spleens and then CD4+ CD25+ T cells were sorted by magnetic bead cell sorting (MACS) system. The purity of CD4+ CD25+ T cells were analyzed by flow cytometry (FCM). The activity of them was detected by trypan blue staining. Interleukin (IL)-2 and IL-10 levels in culture supernatant were determined by enzyme linked immunosorbent assay (ELISA). Results The purity of CD4+ CD25+ T cells sorted by MACS was 83%-96%. There was significant difference in the levels of IL-2 and IL-10 secreted by lymphocytes among CD4+ CD25+ Treg group [ (10.25±3.31), (40.32±8.05) ng/L], CD4+ CD25- T group [(58.21±13.05),(11.52±3.01)ng/L] and mixed culture group [ (39.54±13.82), (31.25±4.36)ng/L (P<0.05,P<0.01).Conclusion High purity of CD4+ CD25+ Treg with immune regulatory function can be isolated by MACS. The immunosuppression of CD4+ CD25+ Treg to CD4+ CD25- T was related to the regulation of IL-10 through IL-2.%目的 探讨小鼠CD4+CD25+T调节细胞(Treg)的分离培养、纯化及其部分功能检测.方法 采用免疫磁珠分离法(MACS)对分离小鼠的脾淋巴细胞进行分选CD4+CD25+Treg细胞,锥虫蓝细胞染色检测其活性,流式细胞仪检测分选所得活性细胞的纯度,酶联免疫吸附试验(ELISA)检测培养上清液中白细胞介素(IL)-2、IL-10水平的浓度.结果 MACS分离的CD4+CD25+Treg细胞的纯度达83%~96%.体外培养中Treg组、T组和混合组IL-2和IL-10的平均水平分别为:(10.25±2.31)、(40.32±8.05)ng/L;(5 8.21±13.05)、(11.52±3.01)ng/L;(39.54±12.82)、(31.25±4.36)ng/L,数据差异有统计学意义(P<0.05,P<0.01).结论 采用MACS系统两步法,可获得高纯度、具有免疫抑制功能的Treg细胞,该细胞对CD4+CD25-T细胞的免疫抑制作用可能是通过IL-10对IL-2的调节作用实现的.

  6. 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.

  7. 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...... observations, this review presents a characterization of the phenotype and functions of the Treg cells in vitro and in vivo. An overview of the surface molecules associated with and the cytokines produced by the Treg cells is given and the origin, activation requirements and mode of action of the Treg cells...... are discussed. Finally, we address the possibility that Treg cells may play a central role in immune homeostasis, regulating not only autoimmune responses, but also immune responses toward foreign antigens....

  8. 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...... of immune homeostasis and self-tolerance by counteracting the development and effector functions of potentially autoreactive T cells. We have in the previous APMIS review described the phenotype and physiology of Treg cells. The present overview deals with the thymic origin of Treg cells and their role...... in disease models such as autoimmune gastritis and inflammatory bowel disease. Finally, we will consider some aspects of the therapeutic potential of Treg cells....

  9. 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...

  10. Dexamethasone Regulates Macrophage and Cd4+Cd25+ Cell Numbers in the Chicken Spleen

    Directory of Open Access Journals (Sweden)

    AS Calefi

    2016-03-01

    Full Text Available Abstract Dexamethasone (DEX is a corticoid hormone that is experimentally used to mimic the effects of increased levels of endogenous corticosterone observed during the stress response. Currently, stress is considered one of the major predisposing factors for diseases in the poultry industry. The aim of this study was to analyze the effects of DEX and/or of a 20-fold coccidial vaccine dose on leukocyte phenotypes in the spleen and cecal tonsils of chickens. Twenty specific-pathogen-free (SPF Leghorn chickens were divided into four groups: a non-treated group (NT, a DEX-treated group (Dex, a vaccinated group (V and a DEX-treated+vaccinated group (Dex+V. On experimental day (ED 42, each bird in the vaccinated groups received a anti-coccidial vaccine. DEX was injected in the birds of the Dex and Dex+V groups (0.9 mg/kg onED42 and ED45. The immunophenotyping was performed by flow cytometry analysis of splenocytes and cecal tonsils cells onED48. DEX treatment per se was unable to change CD4+CD8+, CD4+CD8+ and CD4-CD8+ populations with TCRgd or CD28 in the spleen, or macrophages and T lymphocytes in the cecal tonsils. V group birds presented higher numbers of splenic macrophages compared with those measured in the Dex+V group. The number of CD4+CD25+ cells in the spleen of birds of the V group was higher than those measured in the other experimental groups. Our data suggest that CD4+CD25+ cells and macrophages might be influenced by DEX treatment in spleen, but not in the cecal tonsils of chickens inoculated with Eimeria.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 调节性CD4~+CD25~+T细胞的分离纯化及免疫功能研究%Isolation purification and function analysis of CD4~+CD25~+regulatory T cells

    Institute of Scientific and Technical Information of China (English)

    杨阳; 韩岩; 杨麦贵; 夏炜; 庄然; 郭树忠

    2009-01-01

    Objective To prepare CD4~+CD25~+regulatory T cells (Treg) and analyze their immune function in order to prevent and treat rejection of composite tissue allotransplantation (CTA) by inducing local immunotolence. Methods The CD4~+CD25~ +Treg (1×10~6) were isolated from the rat spleens,and sorted with magnetic bead by magnetic activated cell sorting (MACS) system. The activity of CD4~+CD25~+Treg was assayed by Trypan blue (2% ) staining,and their purity was analyzed by flow cytometry (FCM). The relationship between IL-2 (200 U/ml) and CD4~+CD25~+Treg reactivity to stimuli by CD3 (5 mg/L) antibody was observed. Results The mean activity and purity of CD4~+CD25~+Treg isolated from 8 male rats were (97.90±0.36)% and (96.05±0.41)% respectively. The lower reactivity to CD3 stimuli was found with cultivation inhibition ratio of 89%. IL-2 could reverse the inhibition. Conclusion The CD4~+CD25~+Treg with higher purity can be isolated quickly by MACS, and the cells are anergic immuno-suppression in vitro. This can fit the demand of investigation on animal CTA rejection.%目的 制备调节性CD~+ CD25~+T细胞(Treg)分析其免疫功能,诱导局部免疫耐受防治同种异体复合组织移植(CTA)排斥反应.方法 采用免疫磁珠法(MACS)从雄性大鼠脾脏细胞分离CD4~+CD25~+Treg(1×10~6),2%锥虫蓝染色检测活性、流式细胞术分析其纯度,在5 mg/L抗CD3的刺激下观察其反应性、增殖及其与200 U/ml细胞介素(IL)-2的关系.结果 从8只雄性大鼠脾脏分选出的CD4~+CD25~+Treg活性平均为(97.90±0.36)%及纯度为(96.05±0.41)%,CD3刺激呈低反应,按比例培养抑制率为89%,IL-2可使CD4~+CD25~-抑制逆转.结论 MACS能快速分选出较高纯度的CD4~+CD25~+Treg,并且活性良好在体外具有免疫无能及免疫抑制作用,能满足动物CTA排斥反应研究的需要.

  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. Single base mutation in the pro. alpha. 2(I) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but in-frame pro. alpha. 2(I) chain

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, G.; Prockop, D.J. (Thomas Jefferson Univ., Philadelphia, PA (USA))

    1988-07-01

    Previous observations demonstrated that a lethal variant of osteogenesis imperfecta had two altered alleles for pro{alpha}2(I) chains of type I procollagen. One mutation produced a nonfunctioning allele in that there was synthesis of mRNA but no detectable synthesis of pro{alpha}2(I) chains from the allele. The mutation in the other allele caused synthesis of shortened pro{alpha}2(I) chains that lacked most or all of the 18 amino acids encoded by exon 28. Subclones of the pro{alpha}2(I) gene were prepared from the proband's DNA and the DNA sequence was determined for a 582-base-pair (bp) region that extended from the last 30 bp of intervening sequence 26 to the first 26 bp of intervening sequence 29. Data from six independent subclones demonstrated that all had the same sequence as a previously isolated normal clone for the pro{alpha}2(I) gene except that four subclones had a single base mutation at the 3{prime} end of intervening sequence 27. The mutation was a substitution of guanine for adenine that changed the universal consensus sequence for the 3{prime} splicing site of RNA from -AG- to -GG-. S1 nuclease experiments demonstrated that about half the pro{alpha}2(I) mRNA in the proband's fibroblasts was abnormally spliced and that the major species of abnormal pro{alpha}2(I) mRNA was completely spliced from the last codon of exon 27 to the first codon of exon 29. The mutation is apparently unique among RNA splicing mutations of mammalian systems in producing a shortened polypeptide chain that is in-frame in terms of coding sequences, that is used in the subunit assembly of a protein, and that contributes to a lethal phenotype.

  18. Latency-associated peptide identifies a novel CD4+CD25+ regulatory T cell subset with TGFbeta-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Chen, Mei-Ling; Yan, Bo-Shiun; Bando, Yoshio; Kuchroo, Vijay K; Weiner, Howard L

    2008-06-01

    CD4(+)CD25(+) regulatory T cells (Tregs) are essential for maintaining self-tolerance and immune homeostasis. Here we characterize a novel subset of CD4(+)CD25(+) Tregs that express latency-associated peptide (LAP) on their cell surface (CD4(+)CD25(+)LAP(+) cells). CD4(+)CD25(+)LAP(+) cells express elevated levels of Foxp3 and Treg-associated molecules (CTLA4, glucocorticoid-induced TNFR-related gene), secrete TGFbeta, and express both cell surface TGFbeta and surface receptors for TGFbeta. In vitro, the suppressive function of CD4(+)CD25(+)LAP(+) cells is both cell contact and soluble factor dependent; this contrasts with CD4(+)CD25(+)LAP(-) cells, which are mainly cell contact dependent. In a model of experimental autoimmune encephalomyelitis, CD4(+)CD25(+)LAP(+) cells exhibit more potent suppressive activity than CD4(+)CD25(+)LAP(-) cells, and the suppression is TGFbeta dependent. We further show that CD4(+)CD25(+)LAP(+) cells suppress myelin oligodendrocyte glycoprotein-specific immune responses by inducing Foxp3 and by inhibiting IL-17 production. Our findings demonstrate that CD4(+)CD25(+) Tregs are a heterogeneous population and that the CD4(+)CD25(+) subset that expresses LAP functions in a TGFbeta-dependent manner and has greater in vivo suppressive properties. Our work helps elucidate the ambiguity concerning the role of TGFbeta in CD4(+)CD25(+) Treg-mediated suppression and indicates that LAP is an authentic marker able to identify a TGFbeta-expressing CD4(+)CD25(+) Treg subset.

  19. The alpha-chain of the nascent polypeptide-associated complex binds to and regulates FADD function.

    Science.gov (United States)

    Stilo, Romania; Liguoro, Domenico; di Jeso, Bruno; Leonardi, Antonio; Vito, Pasquale

    2003-04-18

    FADD protein is a critical mediator of signal transduction pathways activated by several members of the TNF-receptor gene superfamily. Recently, an induced proximity model has been proposed to interpret FADD-mediated signaling events. According to this model, FADD facilitates signaling by inducing clusters of effector molecules in proximity of the activated receptor complex. An important corollary of the induced-proximity model is that FADD protein should not form oligomers in the absence of receptor stimulation. Here we show that, in the absence of death receptor stimulation, FADD is found associated to the alpha chain of the nascent polypeptide-associated complex (NAC). Exposure to TNF results in disruption of FADD/NAC complex. Expression of NAC regulates formation of FADD oligomers and modulates FADD-mediated signaling. Thus, our observation indicates that NAC may serve as an intracellular regulator of FADD function.

  20. Changes of CD4+ CD25+ Regulatory T Cells, FoxP3 in Adjuvant Arthritis Rats with Damage of Pulmonary Function and Effects of Tripterygium Glycosides Tablet

    Directory of Open Access Journals (Sweden)

    Wan Lei

    2012-01-01

    Full Text Available Objective. To observe the effects of tripterygium glycosides tablet (TPT on swelling degree, arthritis index (AI, pulmonary function, cytokines, the expression of regulatory T cells (Treg, and Foxp3 in rats of adjuvant arthritis. Methods. Rats were averagely divided into normal control (NC group, model control (MC group, methotrexate (MTX group, and tripterygium glycosides tablet (TPT group. Except for the rats of normal group, the others were intracutaneously injected with 0.1 mL of Freund’s complete adjuvant in the right hindlimb. NC group and MC group were treated with physiological saline. MTX group and TPT group were treated with MTX, TPT, respectively. Results. The levels of swelling degree, AI, the alveolar inflammation integral, TNF alpha (TNF-, and endothelium-1 (ET-1 in MC group were significantly increased (, and the levels of forced vital capacity (FVC, 25% vital capacity of the peak expiratory flow (FEF25, 50% vital capacity of the peak expiratory flow (FEF50, 75% vital capacity of the peak expiratory flow (FEF75, maximum midexpiratory flow (MMF, peak expiratory flow (PEF, interleukin-10 (IL-10, CD4+ CD25+ Treg, and Foxp3 were decreased (. The scores of alveolitis and ET-1 were decreased with treatment of TPT. The levels of FVC, FEF25, FEF50, FEF75, MMF, PEF, IL-10, and CD4+ CD25+ Treg in peripheral blood were increased. The expressions of Foxp3 protein and mRNA in lung tissue were also increased in TPT group. Conclusions. The paw swelling can be inhibited by TPT, and the inflammatory response in lung tissue was also decreased, which is a significant improvement in pulmonary function. The mechanism is probably associated with upregulating the expression of IL-10, Foxp3, and downregulating the level of TNF-.

  1. CD4+CD25+ and CD4+CD25high regulatory T cells in disseminated and localized forms of allergic contact dermatitis: relation to specific cytokines

    Directory of Open Access Journals (Sweden)

    Halina Laudańska

    2011-07-01

    Full Text Available The aim of this study was to evaluate regulatory T lymphocytes (Tregs in the course of allergic contact dermatitis (ACD and to elucidate the role of IL-10 and TGF-b in Tregs activity. Peripheral blood CD4+CD25+ and CD4+CD25high cells were determined by flow cytometry in patients with acute disseminated ACD (‘ad’, n = 36, acute localized ACD (‘al’, n = 26, and disseminated ACD during remission (‘rd’, n = 27 as well as in controls (n = 22. Serum levels of cytokines were measured using ELISA. The mean percentage of CD4+CD25+ and CD4+CD25high cells in patients with ad ACD was significantly higher than in controls (p < 0.01 and the remaining patients (p < 0.05. Both cell populations were significantly elevated in persons with widespread skin lesions (p < 0.05. In ad patients the CD4+CD25+ increased during three weeks of disease, although the significant increase of CD4+CD25high was noted only in the third week. Patients with ad ACD showed a significantly decreased serum level of TGF-b1 as compared with controls and the remaining ACD patients. IL-10 level did not differ between all groups. The elevated population of CD4+CD25high cells in ad ACD patients, and its dependence on the extension of skin lesions, suggest a role of Tregs in regulating the course of ACD. The growing Tregs percentages may indicate their peripheral generation during ACD. The development of lesions despite an increased population of Tregs suggests their functional defect. The role of TGF-b1 in the suppressive activity of Tregs cannot be excluded. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 255–262

  2. 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。

  3. The Phenotypic Characterization of Naturally Occurring Regulatory CD4+CD25+T Cells

    Institute of Scientific and Technical Information of China (English)

    Huanfa Yi; Yu Zhen; Lingling Jiang; Jialin Zheng; Yong Zhao

    2006-01-01

    The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms for the induction and maintenance of T cell tolerance. Recently, much attention has been paid to regulatory T cells (Treg), which play a significant role in maintaining peripheral immune tolerance. So far, there has been no satisfactory advance regarding the surface markers of Treg cells, as none is unique for Treg cells. In this review, we summarize some important molecules expressed in naturally occurring CD4+CD25+ Treg cells(nTreg), including forkhead/winged-helix family transcriptional repressor p3 (Foxp3), the tumor necrosis factor receptor (TNFR) family, CD28/CTLA4 molecules, chemokine receptors, Toll-like receptors (TLRs), membranebound TGF-β and other molecules, such as neuropilin-1, lymphocyte activation gene-3 (LAG)-3 and granzyme.This review provides a collective view on current studies of nTreg cell activation and development related to the expression of molecules and cell phenotype markers, which is important for elucidation of nTreg cell origin,development and function.

  4. Do CD4+ CD25+ immunoregulatory T cells hinder tumor immunotherapy?

    Science.gov (United States)

    Antony, Paul Andrew; Restifo, Nicholas P

    2002-01-01

    After years of banishment from mainstream immunology, the notion that one subset of T cells can exert regulatory effects on other T lymphocytes is back in fashion. Recent work in knockout and transgenic mice has begun to bring molecular definition to our understanding of immunoregulatory CD4+CD25+ T cells (Treg/Th3/Tr1). The identification of the glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18) expressed on T regulatory cells might afford new therapeutic opportunities. Another possible therapeutic intervention could be the blockade of signaling through the molecular pair of tumor necrosis factor-related activation induced cytokine (TRANCE) and receptor activator of NF-kappaB (RANK). Based on the available evidence from experimental mouse tumor models, however, it seems that simply blocking or even eliminating T regulatory function will not be enough to manage established tumors. The challenge for immunotherapists now is to overcome immunosuppression using the knowledge gained through the understanding of T regulatory cell function.

  5. Impairment of Circulating CD4+CD25+GARP+ Regulatory T Cells in Patients with Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Kai Meng

    2014-02-01

    Full Text Available Background: Atherosclerosis (AS is an inflammatory and immune disease. Regulatory T cells (Tregs suppress the activation of T cells and have been shown to play a protective role during the pathogenesis of AS. However, specific markers for Tregs are lacking. Recently, glycoprotein A repetitions predominant (GARP was discovered as a specific marker of activated Tregs, and we therefore utilized GARP as a specific surface marker for Tregs in the current study. Methods: To assess whether GARP+ Tregs are downregulated in patients with acute coronary syndrome (ACS, we examined CD4+CD25+GARP+ T cell frequencies as well as their associated cytokines and suppressive function. Additionally, we compared GARP expression to that of FOXP3, which may be more sensitive as a marker of activated Tregs in patients with ACS. Results: Patients with ACS demonstrated a significant decrease in circulating CD4+CD25+GARP+ Tregs. Moreover, the suppressive function of Tregs and levels of related cytokines were also impaired in ACS patients compared to those with stable angina (SA or normal coronary artery (NCA. Additionally, after TCR stimulation, peripheral blood mononuclear cells (PBMCs from patients with ACS exhibited a decrease in CD4+CD25+GARP+ Tregs. Conclusions: These fnding indicate that circulating CD4+CD25+GARP+ Tregs are impaired in patients withACS. Thus, targeting GARP may promote the protective function of Tregs in ACS.

  6. Analysis of circulating regulatory T cells (CD4+CD25+CD127-) after cryosurgery in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Tong-Guo Si; Jun-Ping Wang; Zhi Guo

    2013-01-01

    This study was performed to assess the response of regulatory T cells (Tregs) following cryosurgery in prostate cancer (PCa) patients by measuring their frequency and immune function.Blood was collected prior to and at 4 and 8 weeks after treatment in 30 patients with high-risk PCa who underwent cryosurgery and from 15 healthy volunteers.Circulating CD4+CD25+CD127-Tregs were isolated.Their frequency was detected by flow cytometry,and immune suppressive function was evaluated by measuring the proliferation of CD4+CD25-T cells cocultured with Tregs.The results showed that the percentage of circulating CD4+CD25+CD127-Tregs was increased in PCa patients compared to healthy volunteers (7.6%±0.73% vs.5.8%±-0.54%,P<0.001).The frequency of circulating CD4+CD25+CD127-Tregs was reduced 4 weeks after cryosurgery compared to before surgery (6.3%±0.58% vs.7.6%±0.73%,P<0.001),and the decrease persisted for 8 weeks.However,the suppressive function of Tregs was increased in eight of 12 patients,which might contribute to cancer recurrence.Then the response of circulating rregs is complicated after cryosurgery for PCa,and further studies are warranted.

  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. Detection and Significance of CD4+CD25+CD127dim Regulatory T Cells in Individuals with Severe Aplastic Anemia

    Directory of Open Access Journals (Sweden)

    Weiwei Qi

    2015-09-01

    Full Text Available Objective: To investigate the relationship between CD4+CD25+CD127dim regulatory T cells (Tregs and immune imbalance in acquired severe aplastic anemia (SAA. Materials and Methods: The quantity of CD4+CD25+CD127dim Tregs in 44 SAA patients and 23 normal controls was measured by flow cytometry. Correlations between Tregs and T cell subsets, dendritic cell (DC subsets, granulocyte counts, and percentage of reticulocytes (RET% were analyzed. Results: The percentage of CD4+CD25+CD127dim Tregs in peripheral blood lymphocytes (PBLs of untreated patients was lower than in recovery patients and normal controls (0.83±0.44% vs. 2.91±1.24% and 2.18±0.55%, respectively, p<0.05. The percentage of CD4+CD25+CD127dim Tregs in CD4+ T lymphocytes of recovery patients was higher than that of untreated patients and normal controls (9.39±3.51% vs. 7.61±5.3% and 6.83±1.4%, respectively, p<0.05. The percentage of CD4+ T lymphocytes in PBLs of untreated patients was lower than in recovery patients and normal controls (13.55±7.37% vs. 31.82±8.43% and 32.12±5.88%, respectively, p<0.05. T cell subset (CD4+/CD8+ ratio was 0.41±0.24 in untreated patients, which was lower than in recovery patients (1.2±0.4 and normal controls (1.11±0.23 (p<0.05. DC subset (myeloid DC/plasmacytoid DC ratio, DC1/DC2 ratio was 3.08±0.72 in untreated patients, which was higher than in recovery patients (1.61±0.49 and normal controls (1.39±0.36 (p<0.05. The percentage of CD4+CD25+CD127dim Tregs in PBLs was positively associated with T cell subset (r=0.955, p<0.01 and negatively associated with DC subset (r=-0.765, p<0.01. There were significant positive correlations between CD4+CD25+CD127dim Tregs/PBL and granulocyte counts and RET% (r=0.739 and r=0.749, respectively, p<0.01. Conclusion: The decrease of CD4+CD25+CD127dim Tregs in SAA patients may cause excessive functioning of T lymphocytes and thus lead to hematopoiesis failure in SAA.

  9. Substitution of cysteine for glycine at residue 415 of one allele of the alpha 1(I) chain of type I procollagen in type III/IV osteogenesis imperfecta.

    Science.gov (United States)

    Nicholls, A C; Oliver, J; Renouf, D V; Keston, M; Pope, F M

    1991-01-01

    We have examined the type I collagen in a patient with type III/IV osteogenesis imperfecta. Two forms of alpha 1(I) chain were produced, one normal and the other containing a cysteine residue within the triple helical domain of the molecule. Cysteine is not normally present in this domain of type I collagen. Peptide mapping experiments localised the mutation to peptide alpha 1(I)CB3 which spans residues 403 to 551 of the triple helix. Subsequent PCR amplification of cDNA covering this region followed by sequencing showed a G to T single base change in the GGC codon for glycine 415 generating TGC, the codon for cysteine. The effect of the mutation on the protein is to delay secretion from the cell, reduce the thermal stability of the molecule by 2 degrees C, and cause excessive post-translational modification of all chains in molecules containing one or more mutant alpha 1(I) chains. The clinical phenotype observed in this patient and the position of the mutation conform to the recent prediction of Starman et al that Gly----Cys mutations in the alpha 1(I) chain have a gradient of severity decreasing from the C-terminus to the N-terminus. Images PMID:1770532

  10. 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...

  11. 特应性皮炎患者外周血CD4+CD25+调节性T细胞的检测%Detection of peripheral CD4+CD25+ regulatory T (Treg) cells in patients with atopic dermatitis

    Institute of Scientific and Technical Information of China (English)

    曾美; 高谦; 何定阳; 陈丽华; 吴国珍

    2010-01-01

    目的 探讨CD4+CD25+节性T细胞(CD4+CD25+Treg)在特应性皮炎(AD)发病中的作用机制及临床意义.方法 流式细胞仪分析AD患者外周血中CD4+CD25+Treg细胞数量,实时荧光定量PCR检测外周血单核细胞(PBMC)中Foxp3 mRNA水平,ELISA检测血清中IL-2、IL-4、IL-10、IFN-γ水平.结果 AD患者外周血中CD4+CD25+Treg细胞占CD3+T细胞及CD4+T细胞的比例均明显低于正常人对照组(t'=3.775、4.533,P值均<0.01);外周血中CD4+CD25+Treg细胞占CD3+T细胞比例在AD患者急性期明显低于慢性期(t=2.217,P<0.05),而在急性期与亚急性期、亚急性期与慢性期之间差异均无统计学意义(t=1.558、0.49,P值均>0.05).AD患者PBMC中Foxp3 mRNA的水平低于正常人对照组(z=-2.368,P<0.05);其外周血中CD4+CD25+Treg细胞与血清中IL-2和IL-10成正相关(r=0.512、0.494,P值均<0.05),与IL-4和IFN-γ的相关性无统计学意义(r=-0.110、-0.237,P值均>0.05).结论 在AD患者中,外周血中CD4+CD25+Treg细胞数量及Foxp3 mRNA水平均下降,从而可能减少对Th2细胞增生及其细胞因子分泌的抑制,使Th2占优势,参与AD的发病.%Objective To explore the action mechanism and clinical significance of CD4+CD25+ regulatory T (Treg) cells in the development of atopic dermatitis (AD). Methods Peripheral blood mononuclear cells (PBMC) were obtained from 46 patients with AD and 20 normal human controls. Flow cytometry was performed to detect the number of CD4+CD25+ Treg cells, real-time fluorescence PCR assay to measure the Foxp3 mRNA level in PBMC, ELISA to determine the serum levels of IL-2, IL-4, IL-10 and IFN-γ. Results A statistical decrease was observed in the percentages of peripheral CD4+CD25+ Treg cells among CD3+ T cells and CD4+ T cells in AD patients compared with normal controls (t' = 3.775, 4.533, both P< 0.01 ), and in the percentage of peripheral CD4+CD25+ Treg cells among CD3+ T cells in patients with acute AD compared with those with chronic AD

  12. 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.

  13. 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.

  14. Sec61alpha synthesis is enhanced during translocation of nascent chains of collagen type IV in F9 teratocarcinoma cells after retinoic acid treatment

    Directory of Open Access Journals (Sweden)

    L.R. Ferreira

    2003-01-01

    Full Text Available Nascent procollagen peptides and other secretory proteins are transported across the endoplasmic reticulum (ER membrane through a protein-conducting channel called translocon. Sec61alpha, a multispanning membrane translocon protein, has been implicated as being essential for translocation of polypeptide chains into the cisterns of the ER. Sec61alpha forms a protein complex with collagen and Hsp47, an ER-resident heat shock protein that binds specifically to collagen. However, it is not known whether Sec61alpha is ubiquitously produced in collagen-producing F9 teratocarcinoma cells or under heat shock treatment. Furthermore, the production and utilization of Sec61alpha may depend on the stage of cell differentiation. Cultured F9 teratocarcinoma cells are capable of differentiation in response to low concentrations of retinoic acid. This differentiation results in loss of tumorigenicity. Mouse F9 cells were grown in culture medium at 37ºC and 43ºC (heat shock treatment treated or not with retinoic acid, and labeled in certain instances with 35S-methionine. Membrane-bound polysomes of procollagen IV were then isolated. Immunoprecipitation and Western blot analysis were performed using polyclonal antibodies against collagen IV, Hsp47 and Sec61alpha. Under retinoic acid-untreated conditions, F9 cells produced undetectable amounts of Sec61alpha. Sec61alpha, Hsp47 and type IV collagen levels were increased after retinoic acid treatment. Heat shock treatment did not alter Sec61alpha levels, suggesting that Sec61alpha production is probably not affected by heat shock. These data indicate that the enhanced production of Sec61alpha in retinoic acid-induced F9 teratocarcinoma cells parallels the increased synthesis of Hsp47 and collagen type IV.

  15. 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.

  16. 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

  17. Autoimmune thyroid disease and CD4~+ CD25~+ regulatory T cell%自身免疫性甲状腺疾病和CD4~+CD25~+调节性T细胞

    Institute of Scientific and Technical Information of China (English)

    侍晓云; 赵勇

    2010-01-01

    自身免疫性甲状腺疾病(AITD)的发生及发展与CD4~+CD25~+调节性T细胞(Treg细胞)的数量和功能密切相关.动物实验证明Treg细胞可抑制AITD的发生.如果清除动物体内的该类细胞,可导致AITD发病或使原有的甲状腺疾病加重,Treg细胞通过抑制效应性T细胞的激活而发挥对AITD的影响作用.无论是胸腺还是外周,不同诱导体系来源的Treg细胞均对AITD有影响作用.%The occurance and development of autoimmune thyroid disease (AITD)is related with changes of quantities and function of CD4~+CD25~+ regulatory T(Treg) cells. Different studies indicated that Treg cells can inhibit the development of AITD. Depletion of Treg cells can improve the incidence of AITD or increase the severity of AITD. Treg cells play roles in inhibiting activation of effector T cell. No matter Treg cells or CD4~+ CD25~+ regulatory T cells generated in the periphery can influence the development of AITD.

  18. Role of CD4 + CD25 + regulatory T cells in the patients with ulcerative colitis%CD4+CD25+T细胞在溃疡性结肠炎患者中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    宋振梅; 王晓娣

    2010-01-01

    目的 研究溃疡性结肠炎(UC)患者外周血CD4+CD25+调节性T细胞和其特异性标志物Foxp3的表达及其在UC不同病期的变化,探讨其在UC发病机制中的意义.方法 研究纳入2007年2月至2008年12月在我院就诊的UC患者40例,其中活动期23例,缓解期17例;同时选择33例肠易激综合征(IBS)患者及32名健康者作为对照.用流式细胞仪检测UC患者、IBS患者和正常对照者的外周血CD4+CD25+T细胞阳性率,用RT-PCR检测外周血单个核细胞(PBMC)中Foxp3 mRNA的表达,用酶联免疫吸附实验检测血清中白细胞介素-10(IL-10)和转化生长因子-β(TGF-β)的浓度.结果 活动期和缓解期UC患者、IBS患者、正常对照者外周血CD4+T细胞总数相比差异无统计学意义(P=0.126).CD4+CD25+T细胞在CD4+T细胞中所占比例在活动期和缓解期UC患者中均明显低于IBS患者和正常对照组(P均<0.01),活动期患者较缓解期患者更低(P<0.001),并且与疾病活动指数(r=-0.660,P<0.001)及红细胞沉降率(r=-0.572,P=0.001)均呈显著负相关,而IBS患者和正常对照者间差异没有统计学意义(P=0.343).PBMC中Foxp3 mRNA的表达在活动期和缓解期UC患者均明显低于IBS患者和正常对照组(P均<0.001).而血清IL-10和TGF-β的浓度在活动期和缓解期UC患者、IBS患者和正常对照者4组间无明显差异(P均>0.05).结论 活动期UC患者外周血CD4+CD25+调节性T细胞明显降低,缓解期UC患者的表达有所升高,并且与临床疾病活动相关,提示这类细胞可能参与了UC疾病的发生发展,Foxp3表达降低可能是导致CD4+CD25+T细胞发育障碍的重要因素.%Objective To investigate the levels of CD4 + CD25 + regulatory T cells and the Foxp3 in the peripheral blood of patients with ulcerative colitis ( UC), and analyze its role in the pathogenesis of UC. Methods From February 2007 to December 2008, 40 UC patients (23 active and 17 remissive), 33 irritable bowel syndrome (IBS

  19. 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.

  20. 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.

  1. 脓毒症患者CD4+CD25+调节性T细胞检测的临床意义%Clinic significance of Testing CD4+CD25+ Treg cells in patients with sepsis

    Institute of Scientific and Technical Information of China (English)

    邵敏; 刘宝; 王锦权; 陶晓根; 周树生; 金魁; 张翠萍

    2011-01-01

    目的 探讨脓毒症患者CD4+CD25+调节性T细胞(Treg)的水平与机体细胞免疫状态的关系及其检测的临床意义.方法 将脓毒症患者40例按照疾病严重程度分为3组:脓毒症组14例,严重脓毒症组15例,脓毒症休克组11例.所有入选的40例脓毒症患者在入选当天行流式细胞术检测血中CD4+CD25+调节性T细胞的比例和CD3+、CD4+、CD8+和CD4+/CD8+水平.比较脓毒症组、严重脓毒症组和脓毒症休克组血中CD4+CD25+调节性T细胞比例变化和CD3+、CD4+、CD8+和CD4+/CD8+水平变化.同时选取20例健康人为对照组.结果 健康对照组CD4+CD25+调节性T细胞表达率脓毒症休克组最高,严重脓毒症组次之,脓毒症组最低,三组间两两比较差异有统计学意义(P<0.05).脓毒症组CD3+、CD4+和CD4+/CD8+较正常对照组明显升高(P<0.05),CD8+较正常对照组差异不明显(P>0.05).严重脓毒症组和脓毒症休克患者CD3+、CD4+、CD4+/CD8+较正常对照组明显降低(P<0.05),CD8+较正常对照组改变不明显(P>0.05).结论 脓毒症患者外周血CD4+CD25+调节性T细胞表达增加,可能导致CD3+、CD4+、CD4+/CD8+水平降低,免疫抑制加强.提示CD4+CD25+调节性T细胞在脓毒症的免疫发病机制中可能起着重要作用,对评估患者预后有临床价值.%Objective To study the level and significance of CD4+CD25+ Treg cells and CD3+、 CD4+、 CD8+ cells in peripheral blood of patients with sepsis. Methods 40 patients with sepsis Patients were divided into three groups: sepsis group(n=14), severe sepsis group(n=l5), and septic shock group (n=11).The expression of CD4+CD25+ Treg cells and CD3+、 CD4+、 CD8+ cells of 40 patients on the day 1 was detected by flow cytometry. The comparision in the expression of CD4+CD25+ Treg cells and CD3+、 CD4+、 CD8+ cells within groups was made. Twenty healthy individuals served as controls. Results The expression rate. The expression of CD4+CD25+ Treg cells was the highest

  2. Fibrinogen geneva II: a new congenitally abnormal fibrinogen alpha chain (Gly17Asp) with a review of similar mutations resulting in abnormal knob A.

    Science.gov (United States)

    Casini, Alessandro; De Maistre, Emmanuel; Casini-Stuppi, Virginie; Fontana, Pierre; Neerman-Arbez, Marguerite; de Moerloose, Philippe

    2014-04-01

    Congenital dysfibrinogenemias are characterized by biosynthesis of a structurally abnormal fibrinogen molecule that exhibits reduced functional levels compared with the level of fibrinogen antigen. To date a large number of mutations have been identified in patients with dysfibrinogenemia. Mutations occurring at the thrombin cleavage site (Arg16-Gly17 in the mature alpha-chain) at the amino-terminal end of the fibrinogen alpha chain are a common cause of the disease. These mutations causing abnormal fibrin polymerization are associated with different phenotypes. Here, we report the identification of a novel heterozygous missense mutation of Glycine 17 (Gly17Asp) in a female patient with mild bleeding manifestations, and compare it with other previously reported mutations also resulting in abnormal knob A.

  3. A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF.

    Science.gov (United States)

    Tavernier, J; Devos, R; Cornelis, S; Tuypens, T; Van der Heyden, J; Fiers, W; Plaetinck, G

    1991-09-20

    cDNA clones encoding two receptor proteins involved in the binding of human interleukin 5 (hIL5) have been isolated. A first class codes for an IL5-specific chain (hIL5R alpha). The major transcript of this receptor gene, as analyzed in both HL-60 eosinophilic cells and eosinophilic myelocytes grown from cord blood, encodes a secreted form of this receptor. This soluble hIL5R alpha has antagonistic properties. A second component of the hIL5R is found to be identical to the beta chain of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) high affinity receptor. The finding that IL5 and GM-CSF share a receptor subunit provides a molecular basis for the observation that these cytokines can partially interfere with each other's binding and have highly overlapping biological activities on eosinophils.

  4. 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

    The consequences of two amino acid polymorphisms of human electron transfer flavoprotein (alpha-T/I171 in the alpha-subunit and beta-M/T154 in the beta-subunit) on the thermal stability of the enzyme are described. The alpha-T171 variant displayed a significantly decreased thermal stability...... thermal stability) was significantly overrepresented. Subgrouping of the VLCAD patients into three phenotypic classes (severe childhood, mild childhood, and adult presentation) revealed that the overrepresentation of the alpha-T171 variant was significant only in patients with mild childhood presentation...

  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. Diving behaviour and haemoglobin function: the primary structure of the alpha- and beta-chains of the sea turtle (Caretta caretta) and its functional implications.

    Science.gov (United States)

    Petruzzelli, R; Aureli, G; Lania, A; Galtieri, A; Desideri, A; Giardina, B

    1996-06-15

    The amino acid sequence of the alpha- and beta-chains of haemoglobin (Hb) from the loggerhead sea turtle (Caretta caretta) has been determined. Comparison with that of human Hb shows differences in several residues involved in both alpha 1 beta 1 and alpha 1 beta 2 packing contacts. On the whole, in spite of the mutations, the essential characteristics of both interfaces seem to be maintained. The functional properties of the sea turtle Hb have been investigated at different temperatures and as a function of proton, chloride and organic phosphate concentrations. In addition to overall similarities shared with most of the vertebrate Hbs previously described, this molecule shows significant differences which could be related to the life behaviour of the turtle. In fact, while the shape of the Bohr-effect curve is well adapted for gas exchange during prolonged dives, the very small enthalpy change for O2 binding ensures that O2 delivery becomes essentially insensitive to the temperature changes of the environment. Moreover, and similarly to the case of emperor penguin Hb, the small alkaline Bohr effect appears to be only choride-linked, since the pH dependence of the O2 affinity is abolished in the absence of this ion. These functional characteristics are discussed on the basis of the primary structure of alpha- and beta-chains.

  7. Effects of IL-7 and IL-2 on CD4+CD25-T cells proliferation in vitro%IL-7联合IL-2对脐血CD4+CD25-T细胞体外诱导扩增影响的研究

    Institute of Scientific and Technical Information of China (English)

    仉洁; 郝京生; 李俊甫; 邢龙龙; 刘志文; 钟理; 刘薇

    2014-01-01

    目的:初步探讨IL-7联合IL-2对脐血CD4+CD25-T细胞体外扩增的促进作用,建立稳定的体外培养扩增脐血CD4+CD25-Tregs的培养体系,比较诱导扩增后的CD4+CD25+Tregs和自然分选的CD4+CD25+Tregs对PBMCs功能活性的影响。方法:采用免疫磁珠分选法分选出脐血CD4+CD25-T细胞和CD4+CD25+T细胞;加入不同浓度的细胞因子IL-7结合适当浓度的IL-2作为诱导剂,分析IL-7体外诱导CD4+CD25-T细胞增殖的有效性及最适浓度。我们利用流式细胞术检测体外扩增后的CD4+CD25-T细胞表型变化;MTS法检测体外诱导扩增的CD4+CD25+Tregs及自然分选的CD4+CD25+Tregs分别对成人外周血中单个核细胞增殖的抑制作用;RT-PCR方法分析体外诱导扩增的CD4+CD25+Tregs 及自然分选的CD4+CD25+Tregs FOXP3基因、IL-10基因和TGF-β基因的cDNA表达的变化。结果:经3周体外培养、各组细胞均有明显的扩增。 IL-7诱导组的扩增最强。体外抑制试验显示体外扩增的Tregs对成人外周血中单个核细胞有明显的抑制作用,IL-7联合IL-2诱导CD4+CD25-T细胞生成的CD4+CD25+Tregs具有较自然分选的CD4+CD25+Tregs稍弱的免疫抑制功能,其中IL-7浓度为4 ng/ml,IL-2浓度为2000 U/ml时诱导CD4+CD25-T细胞生成的CD4+CD25+Tregs杀伤活性最强。结论:成功建立了CD4+CD25+Tregs的体外培养体系,联合应用IL-7、大剂量的IL-2和CD3/CD28单抗是体外诱导扩增CD4+CD25-T细胞成为CD4+CD25+Tregs的优选方法,并且扩增倍数高、可持续高表达CD4及CD25细胞表型。%Objective:To explore the promoting effects of IL-7 and IL-2 on CD4+CD25-T cells proliferation in vitro and construct a stable culture system in vitro for CD 4+CD25+regulatory T cells from human umbilical cord blood.To compare the inhibiting effects between induced proliferated CD 4+CD25+Tregs and naturally isolated CD 4+CD25+Tregs

  8. 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.

  9. 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

  10. Modulation of phenotype and function of human CD4+CD25+ T regulatory lymphocytes mediated by cAMP elevating agents

    Directory of Open Access Journals (Sweden)

    Antonella Riccomi

    2016-09-01

    Full Text Available We have shown that Cholera Toxin (CT and other cyclic AMP (cAMP elevating agents induce up-regulation of the inhibitory molecule CTLA-4 in human resting CD4+ T lymphocytes, which following the treatment acquired suppressive functions. In this study, we evaluated the effect of cAMP elevating agents on human CD4+CD25+ T cells, which include the T regulatory (Treg cells that play a pivotal role in the maintenance of immunological tolerance. We found that cAMP elevating agents induce up-regulation of CTLA-4 in CD4+CD25- and further enhance its expression in CD4+CD25+ T cells. We observed an increase of two isoforms of mRNA coding for the membrane and the soluble CTLA-4 molecules, suggesting that the regulation of CTLA-4 expression by cAMP is at the transcriptional level. In addition, we found that the increase of cAMP in CD4+CD25+ T cells converts the CD4+CD25+Foxp3- T cells in CD4+CD25+Foxp3+ T cells, whereas the increase of cAMP in CD4+CD25- T cells did not up-regulate Foxp3 in the absence of activation stimuli. To investigate the function of these cells, we performed an in vitro suppression assay by culturing CD4+CD25+ T cells untreated or pre-treated with CT with anti-CD3 mAbs-stimulated autologous PBMC. We found that CT enhances the inhibitory function of CD4+CD25+ T cells, CD4+ and CD8+ T cell proliferation and IFNγ production are strongly inhibited by CD4+CD25+ T cells pre-treated with cAMP elevating agents. Furthermore, we found that CD4+CD25+ T lymphocytes pre-treated with cAMP elevating agents induce the up-regulation of CD80 and CD86 co-stimulatory molecules on immature dendritic cells (DCs in the absence of antigenic stimulation, however without leading to full DC maturation. These data show that the increase of intracellular cAMP modulates the phenotype and function of human CD4+CD25+ T cells.

  11. Magnetic cell sorting and flow cytometry sorting methods for the isolation and function analysis of mouse CD4+ CD25+ Treg cells*

    OpenAIRE

    2009-01-01

    Objective: In this paper we compared the two methods of cell sorting (magnetic cell sorting and flow cytometry sorting) for the isolation and function analysis of mouse CD4+ CD25+ regulatory T (Treg) cells, in order to inform further studies in Treg cell function. Methods: We separately used magnetic cell sorting and flow cytometry sorting to identify CD4+ CD25+ Treg cells. After magnetic cell separation, we further used flow cytometry to analyze the purity of CD4+ CD25+ Treg cells, trypan bl...

  12. Reverse effect of CD4+CD25+ regulatory T cells on lupus-like murine%CD4+CD25+调节性T细胞对狼疮样小鼠的干预性研究

    Institute of Scientific and Technical Information of China (English)

    苏虹; 王保龙; 方雪晖; 陈娟; 叶冬青

    2008-01-01

    目的 分析CD4+CD25+调节性T细胞(regulatory T cells,Tregs)对狼疮样小鼠的干预效应,为系统性红斑狼疮(systemic lupus erythematosus,SLE)的免疫干预提供新的思路.方法 采用磁活性标记的细胞分选方法 (magnetic activated cell sorting,MACS)分选BALB/c小鼠CD4+CD25+T细胞,应用流式细胞术(flow cytometry,FCM)检测分选细胞纯度.将6~8 w ♀CB6F1小鼠随机分为3组,包括正常对照组、狼疮鼠模型组(亲代淋巴细胞免疫)、狼疮鼠干预组(亲代淋巴细胞免疫后2 w,输入5×106 Tregs/鼠).分别于诱导后2、4、8、12 w,采用ELISA法检测ANA和抗-dsDNA抗体,并观察肾标本的病理学改变.结果 BALB/c小鼠脾脏单个核细胞经MACS分选后,CD4+CD25+T细胞纯度达98.5%.经亲代淋巴细胞输注后,CB6F1小鼠出现体重降低、皮肤干涩;ANA和抗ds-DNA抗体上升;以及狼疮肾炎的病理学改变.而输入Tregs对已出现自身抗体的狼疮鼠有明显的逆转效应,CB6F1小鼠于输注后抗-dsDNA即开始下降,并伴随其他临床症状和实验室指标的逐渐改善.结论 CD4+CD25+Tregs具有明显的逆转CB6F1鼠狼疮样疾病的效应,将为SLE的免疫干预开辟新途径.

  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. 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.

  15. 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

  16. Evaluation of CD4+ CD25+ FoxP3+ regulatory T cells during treatment of patients with brucellosis.

    Science.gov (United States)

    Hasanjani Roushan, M R; Bayani, M; Soleimani Amiri, S; Mohammadnia-Afrouzi, M; Nouri, H R; Ebrahimpour, S

    2016-01-01

    Cell-mediated immunity (CMI) plays a critical role in the control of brucellosis. Regulatory T cells (Tregs) have a functional character in modulating the balance between host immune response and tolerance, which can eventually lead to chronic infection or relapse. The aim of this study was to assess the alteration of Tregs in cases of brucellosis before and after treatment. Thirty cases of acute brucellosis with the mean age of 41.03±15.15 years (case group) and 30 healthy persons with the mean age of 40.63±13.95 years (control group) were selected and assessed. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of all individuals. We analyzed the alteration of Treg cell count using flow cytometry for CD4, CD25, and FoxP3 markers. The level of CD4+ CD25+ FoxP3+ Treg cells was increased in active patients compared with controls (2.5±0.99% vs 1.6±0.84%, p= 0.0004), but it had declined in the treated cases (1.83±0.73%, p=0.02). The level of Tregs was elevated in three relapsed cases. The frequency of Tregs and Treg/Teff (effector T cell) ratio was correlated with inverse serum agglutination test (SAT) and, 2-mercaptoethanol (2-ME) titers as markers of treatment in brucellosis. Based on our findings, we suggest that regulatory cells, such as CD4+ CD25+ FoxP3+ Treg cells, may contribute to the development of infection processes involving immune responses in brucellosis, and evaluation of regulatory T-cell levels may be a potential diagnostic strategy for the treatment outcome in chronic and relapsed cases of brucellosis.

  17. Increase in TGF-β Secreting CD4+CD25+ FOXP3+ T Regulatory Cells in Anergic Lepromatous Leprosy Patients

    Science.gov (United States)

    Saini, Chaman; Ramesh, Venkatesh; Nath, Indira

    2014-01-01

    Background Lepromatous leprosy caused by Mycobacterium leprae is associated with antigen specific T cell unresponsiveness/anergy whose underlying mechanisms are not fully defined. We investigated the role of CD25+FOXP3+ regulatory T cells in both skin lesions and M.leprae stimulated PBMC cultures of 28 each of freshly diagnosed patients with borderline tuberculoid (BT) and lepromatous leprosy (LL) as well as 7 healthy household contacts of leprosy patients and 4 normal skin samples. Methodology/Principle Findings Quantitative reverse transcribed PCR (qPCR), immuno-histochemistry/flowcytometry and ELISA were used respectively for gene expression, phenotype characterization and cytokine levels in PBMC culture supernatants. Both skin lesions as well as in vitro antigen stimulated PBMC showed increased percentage/mean fluorescence intensity of cells and higher gene expression for FOXP3+, TGF-β in lepromatous (p<0.01) as compared to tuberculoid leprosy patients. CD4+CD25+FOXP3+ T cells (Tregs) were increased in unstimulated basal cultures (p<0.0003) and showed further increase in in vitro antigen but not mitogen (phytohemaglutinin) stimulated PBMC (iTreg) in lepromatous as compared to tuberculoid leprosy patients (p<0.002). iTregs of lepromatous patients showed intracellular TGF-β which was further confirmed by increase in TGF-β in culture supernatants (p<0.003). Furthermore, TGF-β in iTreg cells was associated with phosphorylation of STAT5A. TGF-β was seen in CD25+ cells of the CD4+ but not that of CD8+ T cell lineage in leprosy patients. iTregs did not show intracellular IFN-γ or IL-17 in lepromatous leprosy patients. Conclusions/Significance Our results indicate that FOXP3+ iTregs with TGF-β may down regulate T cell responses leading to the antigen specific anergy associated with lepromatous leprosy. PMID:24454972

  18. 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.

  19. Dendritic cells control CD4+CD25+ Treg cell suppressor function in vitro through juxtacrine delivery of IL-2.

    Directory of Open Access Journals (Sweden)

    Katarina Kulhankova

    Full Text Available CD4(+CD25(+Foxp3(+ regulatory T cells (Tregs restrict inflammatory responses to self and nonself. Aberrant Treg activity is pathologic: Insufficient Treg activity is implicated in autoimmunity, allergy, and graft-versus-host-disease; overabundant activity is implicated in chronic infection and cancer. Tregs require IL-2 for their expansion and acquisition/execution of suppressor function; however, because Tregs cannot produce IL-2, they depend on IL-2 from an exogenous source. Until now, that IL-2 source had not been established. We asked whether dendritic cells (DCs could supply IL-2 to Tregs and, if so, what was required for that delivery. We used flow cytometry, IL-2 ELISPOT, RT-qPCR, and IL-2 promoter-driven reporter assays to measure intracytoplasmic IL-2, secreted protein, IL-2 message and IL-2 promoter activity in bone marrow-derived (BMDC and splenic DCs. We examined conjugate formation between Tregs, conventional CD4(+ cells, and IL-2-expressing DCs. We measured Treg levels of CD25, Foxp3, and suppressor function after co-culture with IL-2 sufficient and IL-2(-/- DCs. We generated IL-2-mCherry-expressing DCs and used epifluorescence microscopy and flow cytometry to track IL-2 transfer to Tregs and test requirements for transfer. Between 0.7 to 2.4% of DCs constitutively produced IL-2 and diverted IL-2 secretion to Tregs by preferentially forming conjugates with them. Uptake of DC IL-2 by Tregs required cell-cell contact and CD25. Tregs increased levels of CD25 and Foxp3 from baseline and showed greater suppressor function when co-cultured with IL-2-sufficient DCs, but not when co-cultured with IL-2(-/- DCs. Exogenous IL-2, added in excess of 500 U/ml to co-cultures with IL-2(-/- DCs, restored Treg suppressor function. These data support a model of juxtacrine delivery of IL-2 from DCs to Tregs and suggest that a subset of DCs modulates Treg function through controlled, spatial delivery of IL-2. Knowledge of how DCs regulate Tregs should

  20. CD4+ CD25+Treg细胞和Th17细胞与寻常型银屑病发病的相关性

    Institute of Scientific and Technical Information of China (English)

    张玉丽

    2011-01-01

    CD4+ CD25+ Treg细胞和Th17细胞是CD4+T细胞的新亚群,参与自身免疫病、感染和肿瘤等疾病的发生发展.研究表明CD4+ CD25+ Treg细胞和Th17细胞与寻常型银屑病的发病密切相关.通过对CD4+ CD25+ Treg细胞和Th17分化发育和功能发挥过程中的关键调节因子进行阻断或加强,可以上调或下调CD4+ CD25+ Treg细胞和Th17在寻常型银屑病中的表达,以用于寻常型银屑病的预防和诊治.

  1. Identifikation und Charakterisierung von Medium Chain Acyl-CoA Dehydrogenase und Myosin Light Chain 4 als neuartige Interaktionspartner des Östrogenrezeptor alpha

    OpenAIRE

    Schanz, Miriam A.

    2012-01-01

    Estrogens (E2) are key regulators of growth, differentiation and physiological processes in various target tissues, including the human heart. E2 exerts its effects mainly through its cognate receptors, e.g.estrogen receptor (ER) α. ERα acts in concert with other interaction partners to mediate estrogenic effects. So far, only few interaction partners of ERα are known in the human myocardium. This project identified Medium Chain Acyl-CoA Dehydrogenase (MCAD) and atrial Myosin Light Chain ...

  2. Heparin binds to the laminin alpha4 chain LG4 domain at a site different from that found for other laminins.

    Science.gov (United States)

    Yamashita, Hironobu; Beck, Konrad; Kitagawa, Yasuo

    2004-01-30

    We previously reported that the LG4 domain of the laminin alpha4 chain is responsible for high-affinity heparin binding. To specify the amino acid residues involved in this activity, we produced a series of alpha4 LG4-fusion proteins in which each of the 27 basic residues (arginine, R; histidine; lysine, K) were replaced one by one with alanine (A). When the effective residues R1520A, K1531A, K1533A, and K1539A are mapped on a structural model, they form a track on the concave surface of the beta-sandwich, suggesting that they interact with adjacent sulfate groups along the heparin chain. Whereas low-affinity heparin-binding sites of other LG domains have been located at the top of the beta-sheet sandwich opposite the N and C termini, the residues for high-affinity heparin binding of alpha4 LG4 reveal a new topological area of the LG module.

  3. 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...

  4. Cytotoxic T Lymphocyte–Associated Antigen 4 Plays an Essential Role in the Function of Cd25+Cd4+ Regulatory Cells That Control Intestinal Inflammation

    OpenAIRE

    Read, Simon; Malmström, Vivianne; Powrie, Fiona

    2000-01-01

    It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25+CD45RBlowCD4+) as those that control autoimmunity. Previous studies have failed to identify how CD25+ Treg cells function in vivo. Our studies reveal that the immune-suppressive func...

  5. DNA Methyltransferase Inhibitor Promotes Human CD4+CD25hFOXP3+ Regulatory T Lymphocyte Induction under Suboptimal TCR Stimulation

    Directory of Open Access Journals (Sweden)

    Chun-Hao Lu

    2016-11-01

    Full Text Available The master transcription factor FOXP3 regulates the differentiation, homeostasis, and suppressor function of CD4+ regulatory T (Treg cells, which are critical in maintaining immune tolerance. Epigenetic regulation of FOXP3 expression has been demonstrated to be important to Treg cell development, but the induction of human Treg cells through epigenetic modification has not been clearly described. We report that the combination of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza and suboptimal T cell receptor (TCR stimulation promoted CD4+CD25hFOXP3+ T cell induction from human CD4+CD25- T cells. 5-Aza treatment enhanced the expression of Treg cell signature genes, CD25, FOXP3, CTLA-4, and GITR, in CD4+CD25h cells. Moreover, 5-Aza-treated CD4+CD25h T cells showed potent suppressive activity in a cell contact-dependent manner and reduced methylation in the Treg-specific demethylated region (TSDR in the FOXP3 gene. The analysis of cytokine production revealed that CD4+CD25- T cells with 5-Aza treatment produced comparable levels of interferon (IFN-γ and transforming growth factor (TGF-β, but less IL-10, and more IL-2 when compared to cells without 5-Aza treatment. The increased IL-2 was indispensible to the enhanced FOXP3 expression in 5-Aza-treated CD4+CD25h cells. Finally, 5-Aza-treated CD4+CD25h T cells could be expanded with IL-2 supplementation alone and maintained FOXP3 expression and suppressor function through the expansion. Our findings demonstrate that DNA demethylation can enhance the induction of human Treg cells and promise to solve one of the challenges with using Treg cells in therapeutic approaches.

  6. 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.

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

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    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.

  8. 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)

  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.

  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. 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.

  16. Targeting of CD25 and glucocorticoid-induced TNF receptor family-related gene-expressing T cells differentially modulates asthma risk in offspring of asthmatic and normal mother mice.

    Science.gov (United States)

    Hubeau, Cedric; Apostolou, Irina; Kobzik, Lester

    2007-02-01

    Immunological mechanisms leading to increased asthma susceptibility in early life remain obscure. In this study, we examined the effects of neonatal Ab treatments targeting T cell populations on the development of an asthma syndrome. We used a model of increased asthma susceptibility where offspring of asthmatic BALB/c mother mice are more prone (than normal pups) to develop the disease. Neonatal pretreatment of naive pups with mAb directed against the IL-2Ralpha chain (CD25), the costimulatory molecule glucocorticoid-induced TNFR family related gene, and the inhibitory molecule CTLA-4 elicited contrasting effects in offspring depending on the mother's asthma status. Specifically, neonatal CD25(high) T cell depletion stimulated asthma susceptibility in normal offspring whereas it ameliorated the condition of pups born of asthmatic mothers. Conversely, glucocorticoid-induced TNFR family related gene ligation as a primary signal reduced the spleen cellularity and largely abrogated asthma susceptibility in asthma-prone offspring, without inducing disease in normal pups. Striking changes in Th1/Th2 cytokine levels, especially IL-4, followed mAb pretreatment and were consistent with the impact on asthma susceptibility. These results point to major differences in neonatal T cell population and responsiveness related to maternal asthma history. Interventions that temporarily remove and/or inactivate specific T cell subsets may therefore prove useful to attenuate early life asthma susceptibility and prevent the development of Th2-driven allergic airway disease.

  17. Anti-CD25 treatment depletes Treg cells and decreases disease severity in susceptible and resistant mice infected with Paracoccidioides brasiliensis.

    Directory of Open Access Journals (Sweden)

    Maíra Felonato

    Full Text Available Regulatory T (Treg cells are fundamental in the control of immunity and excessive tissue pathology. In paracoccidioidomycosis, an endemic mycosis of Latin America, the immunoregulatory mechanisms that control the progressive and regressive forms of this infection are poorly known. Due to its modulatory activity on Treg cells, we investigated the effects of anti-CD25 treatment over the course of pulmonary infection in resistant (A/J and susceptible (B10.A mice infected with Paracoccidioides brasiliensis. We verified that the resistant A/J mice developed higher numbers and more potent Treg cells than susceptible B10.A mice. Compared to B10.A cells, the CD4(+CD25(+Foxp3(+ Treg cells of A/J mice expressed higher levels of CD25, CTLA4, GITR, Foxp3, LAP and intracellular IL-10 and TGF-β. In both resistant and susceptible mice, anti-CD25 treatment decreased the CD4(+CD25(+Foxp3(+ Treg cell number, impaired indoleamine 2,3-dioxygenase expression and resulted in decreased fungal loads in the lungs, liver and spleen. In A/J mice, anti-CD25 treatment led to an early increase in T cell immunity, demonstrated by the augmented influx of activated CD4(+ and CD8(+ T cells, macrophages and dendritic cells to the lungs. At a later phase, the mild infection was associated with decreased inflammatory reactions and increased Th1/Th2/Th17 cytokine production. In B10.A mice, anti-CD25 treatment did not alter the inflammatory reactions but increased the fungicidal mechanisms and late secretion of Th1/Th2/Th17 cytokines. Importantly, in both mouse strains, the early depletion of CD25(+ cells resulted in less severe tissue pathology and abolished the enhanced mortality observed in susceptible mice. In conclusion, this study is the first to demonstrate that anti-CD25 treatment is beneficial to the progressive and regressive forms of paracoccidioidomycosis, potentially due to the anti-CD25-mediated reduction of Treg cells, as these cells have suppressive effects on the

  18. 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

  19. 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

  20. PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells.

    Science.gov (United States)

    Wang, Wenshi; Lau, Roy; Yu, Daohai; Zhu, Weiwei; Korman, Alan; Weber, Jeffrey

    2009-09-01

    Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. However, the underlying mechanisms by which they impact antigen-specific CD8(+) immune responses in cancer patients and how they interact with each other under physiologic conditions remain unclear. Herein, we examined the relationship of PD-1 and its abrogation to the function of Treg in patients with melanoma using short-term in vitro assays to generate melanoma-specific T cells. We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. Programmed death ligand (PD-L) 1 expression was also detected on patients' Treg. PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. PD-1 blockade also resulted in down-regulation of intracellular FoxP3 expression by Treg. These data suggest that PD-1 is importantly implicated in the regulation of Treg function in melanoma patients.

  1. 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.

  2. CD25(+) Bcl6(low) T follicular helper cells provide help to maturing B cells in germinal centers of human tonsil.

    Science.gov (United States)

    Li, Haishan; Pauza, C David

    2015-01-01

    The majority of CXCR5(+) PD1(+) CD4(+) T follicular helper (Tfh) cells (>90%) are CD25(-) Bcl6(hi) , while a small subpopulation (<10%) are CD25(+) Bcl6(low) but do not express FoxP3 and are not T regulatory cells. We purified T:B-cell conjugates from tonsils and found they were enriched for the CD25(+) Bcl6(low) Tfh-cell subpopulation. In response to IL-2, these CD25(+) Tfh cells increased expression of costimulatory molecules ICOS or OX40, upregulated transcription factor cMaf, produced cytokines IL-21, IL-17, and IL-10, and raised the levels of antiapoptotic protein Bcl2. Conjugates formed with CD25(+) BCl6(low) Tfh cells included B cells expressing higher levels of activation-induced cytidine deaminase (AID), memory marker CD45RO, surface IgG or IgA, and MHC class II compared to B-cell conjugates including CD25(-) Bcl6(hi) Tfh cells. While IL-2 suppresses early Tfh-cell differentiation, Tfh-cell recognition of antigen-presenting B cells and signaling through the T-cell receptor likely triggers expression of the high-affinity IL-2 receptor and responses to IL-2 including downregulation of Bcl6. CD25 expression on Tfh cells and local production of IL-2 in tonsil or lymph node may support B helper T-cell function during later stages of B-cell maturation and the development of immune memory.

  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. High proportions of FOXP3+CD25high T cells in neonates are positively associated with allergic sensitization later in childhood

    Science.gov (United States)

    Strömbeck, A; Rabe, H; Lundell, A-C; Andersson, K; Johansen, S; Adlerberth, I; Wold, A E; Hesselmar, B; Rudin, A

    2014-01-01

    Background The role of FOXP3+ regulatory T cells in the prevention against sensitization and allergy development is controversial. Objective We followed 65 newborn Swedish children from farming and non-farming families from birth to 3 years of age and investigated the relation between CD4+ T cell subsets in blood samples and development of sensitization and allergic disease. Methods The proportions of FOXP3+CD25high, CTLA-4+CD25+, CD45RO+, HLA-DR+, CCR4+ or α4β7+ within the CD4+ T cell population were examined by flow cytometry of blood samples at several time-points. Mononuclear cells were isolated from blood and stimulated with birch allergen, ovalbumin or the mitogen PHA, and the levels of IL-1β, IL-6, TNF, IFN-γ, IL-5 and IL-13 were measured. A clinical evaluation regarding the presence of allergen-specific IgE and allergy was performed at 18 and 36 months of age. Results Multivariate discriminant analysis revealed that children who were sensitized at 18 or 36 months of age had higher proportions of FOXP3+CD25high T cells at birth and at 3 days of life than children who remained non-sensitized, whereas allergy was unrelated to the neonatal proportions of these cells. The proportions of CTLA-4+CD25+ T cells were unrelated to both sensitization and allergy. The association between higher proportions of FOXP3+CD25high T cells and sensitization persisted after exclusion of farmer's children. Finally, a farming environment was associated with lower proportions of FOXP3+CD25high T cells in early infancy and to a more prominent T cell memory conversion and cytokine production. Conclusion & Clinical Relevance Our results indicate that high proportions of FOXP3+CD25high T cells in neonates are not protective against later sensitization or development of allergy. PMID:24528482

  5. 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....

  6. Characterization of regulatory T cells identified as CD4+CD25highCD39+ in patients with active tuberculosis

    Science.gov (United States)

    Chiacchio, T; Casetti, R; Butera, O; Vanini, V; Carrara, S; Girardi, E; Di Mitri, D; Battistini, L; Martini, F; Borsellino, G; Goletti, D

    2009-01-01

    Forkhead box P3 (FoxP3) is a transcription factor whose expression characterizes regulatory T cells (Treg), but it is also present on activated T cells, thus hindering correct Treg identification. Using classical markers for Treg recognition, discordant results were found in terms of Treg expansion during active tuberculosis (TB) disease. Recently CD39 has been shown to be an accurate marker for Treg detection. The objectives of this study were: (i) to identify Treg expressing CD39 in patients with TB and to compare the results with those obtained by the standard phenotypic markers; (ii) to evaluate if Treg are expanded in vitro by exogenous interleukin (IL)-2 or by antigen-specific stimulation; and (iii) to characterize Treg function on the modulation of antigen-specific responses. We enrolled 13 patients with pulmonary TB and 12 healthy controls. Treg were evaluated by flow cytometry ex vivo and after antigen-specific in vitro stimulation using CD25, FoxP3, CD127 and CD39 markers. Results indicate that CD39+ cells within the CD4+CD25high cells have Treg properties (absence of interferon-γ production and transforming growth factor-β1 release upon stimulation). Ex vivo analysis did not show significant differences between TB patients and controls of Treg by classical or novel markers. In contrast, a significantly higher percentage of Treg was found in TB patients after antigen-specific stimulation both in the presence or absence of IL-2. Depletion of CD39+ Treg increased RD1-specific responses significantly. In conclusion, CD39 is an appropriate marker for Treg identification in TB. These results can be useful for future studies to monitor Mycobacterium tuberculosis-specific response during TB. PMID:19438599

  7. 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.

  8. Study on the in vitro expansion of CD4+CD25+ regulatory T cells by mouse dendritic cells%树突状细胞体外扩增小鼠CD4+CD25+调节性T细胞的研究

    Institute of Scientific and Technical Information of China (English)

    罗珊; 李尚为; 靳松; 李小红; 姬巧云

    2013-01-01

    目的 探讨利用小鼠同种异型骨髓源性树突状细胞(BMDC)与CD4+T细胞共培养体外扩增CD4+CD25+调节性T(CD4+CD25+Treg)细胞的方法.方法 将小鼠同种异型imBMDC与CD4+T细胞共培养,通过测定细胞增殖率和CD4+CD25+Treg细胞占CD4+T细胞比例的变化评定该方法体外扩增CD4+CD25+Treg细胞的能力;利用荧光定量RT-PCR检测体外扩增CD4+CD25+Treg细胞FOXP3基因表达及细胞增殖抑制实验检测其细胞功能活性.结果 共培养d7细胞增殖率(5.26±0.286)倍;CD4+CD25+Treg细胞占CD4+T细胞的(33.77±3.69)%,较新鲜分离小鼠脾细胞中CD4+CD25+Treg细胞比例明显增加(P<0.05).体外扩增CD4+CD25+Treg细胞FOXP3基因的表达与新鲜分离CD4+CD25+Treg细胞差异无统计学意义(P>0.05).混合淋巴细胞培养证实体外扩增CD4+CD25+Treg细胞的细胞增殖抑制作用较新鲜分离的CD4+CD25+Treg细胞更强(P<0.05).结论 小鼠同种异型BMDC与CD4+T细胞共培养能有效诱导扩增CD4+CD25+Treg细胞并保持其免疫细胞功能活性.

  9. 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.

  10. 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.

  11. 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

  12. EntransterTM纳米载体介导大鼠角膜CD25siRNA转染的效果及安全性评估%The efficiency and safety assessment of EntransterTM nanoparticle carrier for CD25 siRNA transfection in rat cornea

    Institute of Scientific and Technical Information of China (English)

    秦琴; 石韵洁; 赵敏

    2016-01-01

    背景 基因转染是多种眼病基因治疗的有效方法,理想的非病毒载体是研究角膜基因治疗的关键因素,选择高转染率、基因高表达、低毒性的非病毒载体是成功实施基因治疗的前提. 目的 探讨EntransterTM、脂质体非病毒载体对正常SD大鼠角膜转染CD25 siRNA的转染率和安全性,筛选角膜基因转染的最佳载体.方法 应用随机数字表法将80只雄性SPF级成年SD大鼠随机分为EntransterTM-CD25 siRNA 组、脂质体-CD25 siRNA组、单纯CD25 siRNA组和生理盐水组,每组20只,均以右眼作为实验眼.实验眼眼表麻醉后刮除角膜上皮,按照分组不同分别用EntransterTM-CD25 siRNA、脂质体-CD25 siRNA、单纯CD25siRNA和生理盐水各50μl点眼.于点眼后12h、24 h、3d和7d在裂隙灯显微镜下观察大鼠眼表组织反应,检查各组大鼠角膜表面绿色荧光个数.分别于上述时间点处死各组大鼠各4只并获取角膜组织,采用苏木精-伊红染色法行角膜组织病理学检查;采用罗丹明染色行荧光检测,评估各组大鼠角膜基因转染的转染率;采用TUNEL染色法检测实验眼角膜细胞的凋亡情况以评估各种转染载体的安全性;采用免疫荧光技术检测角膜组织中CD11b的表达. 结果 EntransterTM-CD25 siRNA组大鼠角膜表面的荧光染色数量及强度明显高于脂质体-CD25 siRNA组,单纯CD25 siRNA组大鼠角膜荧光染色出现早,但转染后24 h角膜荧光染色消失.角膜组织病理学检查显示,各组大鼠行基因转染后脂质体-CD25 siRNA组大鼠角膜上皮水肿和角膜炎性细胞浸润程度较EntransterTM-CD25 siRNA组、单纯CD25 siRNA组和生理盐水组严重,角膜基质层和内皮层未发现异常,脂质体-CD25 siRNA组大鼠角膜炎性细胞数明显多于EntransterTM-CD25 siRNA组、单纯CD25 siRNA组和生理盐水组,差异均有统计学意义(均P=0.00).TUNEL检测发现,基因转染后12h和3d,脂质体-CD25siRNA组大鼠角

  13. Evaluation of CD4+CD25+ T lymphocyte response time kinetics in patients with chronic Chagas disease after in vitro stimulation with recombinant Trypanosoma cruzi antigens

    Directory of Open Access Journals (Sweden)

    Suellen Carvalho de Moura Braz

    2013-05-01

    Full Text Available Introduction CD4+CD25+ T lymphocytes have been implicated in the regulation of host inflammatory response against Trypanosoma cruzi, and may be involved in the clinical course of the disease. Methods Peripheral blood mononuclear cells from patients with chronic Chagas disease were cultured in the presence of T. cruzi recombinant antigens and assayed for lymphocytes at distinct time points. Results It was possible to differentiate clinical forms of chronic Chagas disease at days 3 and 5 according to presence of CD4+CD25+ T cells in cell cultures. Conclusions Longer periods of cell culture proved to be potentially valuable for prospective evaluations of CD4+CD25+ T lymphocytes in patients with chronic Chagas disease.

  14. 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.

  15. Study of the Expression of CD4 + CD25 + T Cell and Soluble Cytokines of Peripheral Blood in the Cases of Multiple Sclerosis%多发性硬化患者外周血CD4+CD25+T细胞与可溶性细胞因子表达的相关性研究

    Institute of Scientific and Technical Information of China (English)

    方宇; 张璐; 连亚军; 魏建科; 吴天文; 罗志毅

    2011-01-01

    CD4+ CD25+T细胞和可溶性细胞因子在多发性硬化(multiple sclerosis,MS)发生和发展中起重要作用.本文通过探讨MS患者外周血CD4+ CD25+T细胞数量及可溶性细胞因子与MS病情的关系,为进一步研究MS的发病机制和采取有效治疗措施奠定了基础.%CD4 + CD25+ T cell and soluble cytokines play a critical role during an acute inflammatory attack in multiple sclerosis! MS). In this study, we investigated the relationship between the blood serum levels of CD4 + CD25+ T cell, soluble cytokines and the state of MS. The results would assist in promoting effective therapies and would elucidate pathophysiologic mechanisms relevant to MS.

  16. CD25+CD127+Foxp3- Cells Represent a Major Subpopulation of CD8+ T Cells in the Eye Chambers of Normal Mice

    Science.gov (United States)

    Ziółkowska, Natalia; Ziółkowski, Hubert; Małaczewska, Joanna

    2017-01-01

    The aim of this study has been to determine whether eye chambers constitute part of the normal migratory pathway of naive CD4+ and CD8+ T cells in mouse and if natural CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+ regulatory T cells are present within these eye compartments. To this aim, the cells obtained from aqueous humor (AH) of normal mice were phenotyped in terms of the expression CD4, CD8, CD25, CD127 and transcription factor Foxp3. The mean percentage of CD8+ T cells in the total AH lymphocyte population was as high as 28.69%; the mean percentage of CD8high and CD8low cells in this population was 34.09% and 65.91%, respectively. The presence of cells with the regulatory phenotype, i.e. CD25+Foxp3+ cells, constituted only 0.32% of CD8+ T cell subset. Regarding the expression of CD25, AH CD8+ T cells were an exceptional population in that nearly 85% of these cells expressed this molecule without concomitant Foxp3 expression. Despite having this phenotype, they should not be viewed as activated cells because most of them co-expressed CD127, which indicates that they are naive lymphocytes. With regard to the markers applied in the present research, CD8+CD25+CD127+Foxp3- T cells represent the most numerous subset of AH CD8+ cells. The results suggest that eye chambers in mice are an element in the normal migratory pathway of naive CD8+ T cells. The study presented herein demonstrated only trace presence of CD4+ cells in the eye chambers, as the mean percentage of these cells was just 0.56. Such selective and specific homing of CD8+ and CD4+ cells to the eye chambers is most clearly engaged in the induction and maintenance of ocular immune privilege. PMID:28081241

  17. Three cases of congenital dysfibrinogenemia in unrelated Chinese families: heterozygous missense mutation in fibrinogen alpha chain Argl6His.

    Science.gov (United States)

    Luo, Meiling; Deng, Donghong; Xiang, Liqun; Cheng, Peng; Liao, Lin; Deng, Xuelian; Yan, Jie; Lin, Faquan

    2016-09-01

    Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by an abnormal fibrinogen molecule structure, leading to dysfunctional blood coagulation. This study describes 3 cases of dysfibrinogenemia identified in the unrelated Chinese pedigrees.Routine coagulation screening tests were performed on the probands and their families. The antigens and functionality of fibrinogen was measured using an immunoturbidimetry assay and the Clauss method, respectively. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed using PCR amplification and direct sequencing. The presence of the mutant chains was determined using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. Purified plasma fibrinogen of 3 probands was analyzed using SDS-PAGE, fibrinogen clottability, fibrin polymerization, fibrinopeptide release, and scanning electron microscopy (SEM).The 3 probands had a long thrombin time. Levels of functional fibrinogen were found to be very low, while the fibrinogen antigen was within the normal range. DNA sequencing revealed a heterozygous Arg16His substitution in the fibrinogen Aα chain (FGA). The mutant chains were found to be expressed using MALDI-TOF mass spectroscopy. SDS-PAGE did not reveal any difference in the molecular weights of 3 polypeptide chains between normal and abnormal fibrinogens. Fibrinogen clottability showed a slower fibrin clot formation than the healthy control. Fibrin polymerization, after addition of thrombin, showed a prolonged lag phase and decreased final turbidity. The kinetics of fibrinopeptides release revealed a decreased amount of the released fibrinopeptide A. SEM of the patient's fibrin clot was found to be abnormal.Results indicate that the 3 probands with dysfibrinogenemia were caused by mutations of Aα chain Arg16His. Mutation of this fibrinogen induced dysfunction of plasma fibrinogen.

  18. 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

  19. 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

    for the cloning and sequencing of the cDNA. We found only one class II alpha chain transcript, which bears the major features of a classical class II alpha sequence, including the critical peptide-binding residues. The chicken sequence is more similar to human DR than to the DQ, DP, DO or DM isotypes, most......In mammals, there are MHC class II molecules with distinctive sequence features, such as the classical isotypes DR, DQ and DP. These particular isotypes have not been reported in non-mammalian vertebrates. We have isolated the class II (B-L) alpha chain from outbred chickens as the basis...... 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...

  20. 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.

  1. 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。

  2. CD4+CD25+调节性T细胞对人外周血内皮祖细胞增殖、迁移、黏附的影响%The effect of CD4+CD25+ regulatory T cells on the proliferation,migration and adhesion of endothelial progenitor cells

    Institute of Scientific and Technical Information of China (English)

    谢培益; 苏又苏; 汤海燕; 方红成; 何少林; 李大主

    2011-01-01

    目的:研究CD4+CD25+调节性T细胞对体外培养的人外周血内皮祖细胞(EPCs)增殖、迁移、黏附的影响.方法:密度梯度离心法分离培养人外周血单个核细胞,经FITC-UEA-I和Dil-acLDL双染色鉴定为正在分化的EPCs.进一步采用流式细胞仪检测其表面标志CD34、CD133.磁性细胞分离器(MACS)分离CD4+CD25+调节性T细胞及CD4+CD25-T细胞.将EPCs分别与CD4+CD25+调节性T细胞或CD4+CD25-T细胞共培养36 h.采用MTT比色法、transwell小室、细胞计数法观察EPCs增殖、迁移、黏附能力.结果:与对照组和CD4+CD25-T细胞相比,与CD4+CD25+调节性T细胞共培养EPCs增殖、迁移、黏附能力显著增强,且呈浓度依赖性增强.结论:CD4+CD25+调节性T细胞可显著促进EPCs增殖、迁移、黏附能力,此作用可能是其抗AS作用机制之一.%Objective:To investigat the effect of CD4+CD25+ regulatory T cells (Tregs) on the proliferation,migration and adhesion of endothelial progenitor cells (EPCs) from human circulating blood in vitro. Method : Tregs were isolated from lymphocyte suspensions by magnetic cell sorting column and analyzed by flow cytometry. Human blood mononuclear cells were isolated with Ficoll by density gradient centrifugation. EGM-2MV culture fluid was added, and then cells were plated on dishes coated with human fibronectin. After 7 days, the cells were identified with immunofluorescence and flow cytometry. The cells were cultured alone (control groups), with CD4+CD25- T cells (CD25- groups), or CD4+ CD25+ Tregs (Tregs groups) for 36 hours. The proliferation,migration and adhesion activities of EPCs were determined with MTT assay, transwell assay and adhesive assay, respectively. Result:Compared with control groups and CD25- groups, the proliferative, migratory and adhesive activities of EPCs were significantly enhanced after treated with CD4 + CD25 + Tregs (P<0.05 and P<0. 01). Moreover, the proliferative, migratory and adhesive activities of

  3. Substitution of arginine for glycine at position 154 of the {alpha}1 chain of type I collagen in a variant of osteogenesis imperfecta: Comparison to previous cases with the same mutation

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, J.; Tromp, G.; Kuivaniemi, H.; Prockop, D.J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Castells, S. [Univ. Hospital of Brooklyn, NY (United States)

    1996-01-11

    A substitution of arginine for glycine at amino acid position 154 of the {alpha}1(I) collagen chain was found in a father and his three children. The phenotype of the patients includes manifestations of types I and III/IV osteogenesis imperfecta, but appears to be milder than that of the previously described two unrelated patients that had the identical mutation in the {alpha}1(I) collagen chain. The variability in the phenotype raises the possibility of epistatic loci or environmental effects on expression of the disorder. 35 refs., 3 figs., 2 tabs.

  4. ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) is a new acute-phase protein isolated from cattle during experimental infection

    DEFF Research Database (Denmark)

    Pineiro, M.; Andres, M.; Iturralde, M.;

    2004-01-01

    We have isolated from calf serum a protein with an apparent M, of 120,000. The protein was detected by using antibodies against major acute-phase protein in pigs with acute inflammation. The amino acid sequence of an internal fragment revealed that this protein is the bovine counterpart of ITIH4......, the heavy chain 4 of the inter-alpha-trypsin inhibitor family. The response of this protein in the sera was determined for animals during experimental bacterial and viral infections. In the bacterial model, animals were inoculated with a mixture of Actinomyces pyogenes, Fusobacterium necrophorum....... Because of the significant induction of the protein in the animals in the mastitis and BRSV infection models, we can conclude that ITIH4 is a new positive acute-phase protein in cattle....

  5. 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.

  6. 耐多药结核患者外周血CD4+CD25+Foxp3+T细胞的变化%Change of the peripheral blood CD4+CD25+Foxp3+T cells in patients with multidrug-resistant tuberculosis

    Institute of Scientific and Technical Information of China (English)

    徐传财; 解卫平; 戴冠群; 谈绮; 闵锐; 王虹

    2011-01-01

    目的:探讨CD4+CD25+Foxp3+T细胞在耐多药结核(multidrug-resistant TB,MDR-TB)发病机制中的作用.方法:随机选择MDR-TB患者31例,药物敏感性结核(drug-susceptible TB,S-TB)33例,健康对照(healthy control,HC)30例,流式细胞仪检测外周血CD4+CD25+Foxp3+T细胞.结果:S-TB患者外周血CD4+CD25+Foxp3+T细胞约占CD4+T细胞的(2.43±0.69)%,显著高于健康人的(1.61±0.46)%,两组之间差异具有显著统计学意义;MDR-TB患者外周血CD4+CD25+Foxp3+T细胞约占CD4+T细胞的(3.14±0.59)%,显著高于S-TB患者的细胞比例,两组之间差异具有显著统计学意义.结论:MDR-TB患者外周血CD4+CD25+Foxp3+T细胞明显增加,揭示其在MDR-TB发病中发挥了重要作用.%Objective :To observe the changes of CD4+CD25+Foxp3+T cells in patients with multidrug-resistant tuberchlosis(TB).Methods:We recruited 31 multidrug-resistant TB (MDR-TB) patients,33 drug-susceptible TB (S-TB) patients and 30 healthy controls.Flow cytometry was used to determined the quantity of CD4+CD25+Foxp3+ir cells in the peripheral blood. Results:The mumber of CD4+CD25+Foxp3+T cell in the peripheral blood of patients with S-TB was(2.43±0.69)% of peripheral CD4+ T cell, it was significantly higher than heathy controls [ ( 1.61±0.46) % ] and lower than patients with MDR-TB [ (3.14±+0.59) % ]. Conclusion: CD4+CD25+Foxp3+T cells increased in MDR-TB patients significantly, this suggests that CD4+CD25+Fox3+T cells play an important role in the pathogenesis of MDR-TB.

  7. Naturally occurring lung CD4(+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-beta.

    Science.gov (United States)

    Joetham, Anthony; Takeda, Katsuyuki; Takada, Katsuyuki; Taube, Christian; Miyahara, Nobuaki; Matsubara, Shigeki; Matsubara, Satoko; Koya, Toshiyuki; Rha, Yeong-Ho; Dakhama, Azzeddine; Gelfand, Erwin W

    2007-02-01

    Peripheral tolerance to allergens is mediated in large part by the naturally occurring lung CD4(+)CD25(+) T cells, but their effects on allergen-induced airway responsiveness have not been well defined. Intratracheal, but not i.v., administration of naive lung CD4(+)CD25(+) T cells before allergen challenge of sensitized mice, similar to the administration of the combination of rIL-10 and rTGF-beta, resulted in reduced airway hyperresponsiveness (AHR) and inflammation, lower levels of Th2 cytokines, higher levels of IL-10 and TGF-beta, and less severe lung histopathology. Significantly, CD4(+)CD25(+) T cells isolated from IL-10(-/-) mice had no effect on AHR and inflammation, but when incubated with rIL-10 before transfer, suppressed AHR, and inflammation, and was associated with elevated levels of bronchoalveolar lavage TGF-beta levels. By analogy, anti-TGF-beta treatment reduced regulatory T cell activity. These data identify naturally occurring lung CD4(+)CD25(+) T cells as capable of regulating lung allergic responses in an IL-10- and TGF-beta-dependent manner.

  8. Activation of the aryl hydrocarbon receptor reduces the number of precursor and effector T cells, but preserves thymic CD4(+)CD25(+)Foxp3(+) regulatory T cells

    NARCIS (Netherlands)

    Schulz, V.J.; Smit, J.J.; Bol-Schoenmakers, M.; van Duursen, M.B.M.; van den Berg, M.; Pieters, R.H.H.

    2012-01-01

    Aryl hydrocarbon receptor (AhR) activation suppresses immune responses, including allergic sensitization, by increasing the percentage of regulatory (Treg) cells. Furthermore, AhR activation is known to affect thymic precursor T cells. However, the effect of AhR activation on intrathymic CD4(+)CD25(

  9. 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

  10. 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 (Gert); 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

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

    Science.gov (United States)

    Nolte-'t Hoen, Esther N M; Boot, Elmieke P J; Wagenaar-Hilbers, Josée P A; van Bilsen, Jolanda H M; Arkesteijn, Ger J A; Storm, Gert; Everse, Linda A; van Eden, Willem; Wauben, Marca 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, we show that CD134 (OX40) can be used as a discriminatory marker combined with CD25 to isolate and characterize viable CD4+ effector cells and Tregs. Before and during adjuvant arthritis in rats, coexpression of CD134 and CD25 identified activated Tregs consistently, as these T cells proliferated poorly to disease-associated antigens and were suppressive in vitro and in vivo. Depending on the time of isolation and location, CD4+ T cell populations expressing CD134 or CD25 contained effector/memory T cells. Analysis of the function, phenotype, and amount of the CD4+ T cell subsets in different lymph node stations revealed spatiotemporal differences in effector cell and Treg compartments during experimental arthritis.

  12. 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,

  13. The dysfunction of CD4(+CD25(+ regulatory T cells contributes to the abortion of mice caused by Toxoplasma gondii excreted-secreted antigens in early pregnancy.

    Directory of Open Access Journals (Sweden)

    Jin-ling Chen

    Full Text Available Toxoplasma gondii is an opportunistic intracellular parasite that is highly prevalent in human and warm-blooded animals throughout the world, leading to potentially severe congenital infections. Although the abortion caused by T. gondii is believed to be dependent on the timing of maternal infection during pregnancy, the mechanism remains unclear. This study was focused on the effects of T. gondii excreted-secreted antigens on pregnant outcomes and CD4(+CD25(+ Foxp3(+ regulatory T cells at different stages of pregnancy. The results showed that in mice the frequency and suppressive function of CD4(+CD25(+ regulatory cells were diminished after injection of T. gondii excreted-secreted antigens at early and intermediate stages of pregnancy. The abortion caused by T. gondii excreted-secreted antigens at early pregnancy could be partly prevented by adoptively transferring of CD4(+CD25(+ cells from the mice injected with T. gondii excreted-secreted antigens at late pregnancy, but not from the mice with the same treatment at early pregnancy. Furthermore, T. gondii excreted-secreted antigens induced apoptosis of CD4(+CD25(+ regulatory cells of mice in early and intermediate stages of pregnancy by down-regulating their Bcl-2 expressions and Bcl-2/Bax ratio. This study provides new insights into the mechanism that T. gondii infection is the high risk factor for abortion in early pregnancy.

  14. Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells.

    NARCIS (Netherlands)

    Coenen, J.J.A.; Koenen, H.J.P.M.; Rijssen, E. van; Hilbrands, L.B.; Joosten, I.

    2006-01-01

    The immunosuppressive drugs rapamycin and cyclosporin A (CsA) are widely used to prevent allograft rejection. Moreover, they were shown to be instrumental in experimental models of tolerance induction. However, it remains to be elucidated whether these drugs have an effect on the CD4+ CD25+ regulato

  15. 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

  16. Increase in circulating CD4CD25Foxp3 T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

    DEFF Research Database (Denmark)

    Riley, C.H.; Morten Krogh, Jensen; Brimnes, M.K.;

    2011-01-01

    have been reported in both hematologic and solid cancers. We have analyzed the number, phenotype, and function of circulating CD4 CD25Foxp3 T cells in patients with chronic myeloproliferative neoplasms. Surprisingly, we found a marked expansion of this subset of lymphocytes in patients treated with IFN...

  17. Chronic Brucellosis Patients Retain Low Frequency of CD4+ T-Lymphocytes Expressing CD25 and CD28 after Escherichia coli LPS Stimulation of PHA-Cultured PBMCs

    Directory of Open Access Journals (Sweden)

    Panagiotis Skendros

    2008-01-01

    Full Text Available Chronic brucellosis patients display a defective Th1 response to PHA. We have previously shown that heat-killed B. abortus (HKBA can downregulate the PHA-induced increase of CD4+/CD25+ and CD14+/CD80+ cells of brucellosis patients. In the present study, we investigate the effect of E. coli LPS, as a potent stimulant of monocytes and autologous T-lymphocytes, on the PHA-cultured PBMCs of the same groups of patients. Thirteen acute brucellosis (AB patients, 22 chronic brucellosis (CB patients, 11 “cured” subjects, and 15 healthy volunteers were studied. The percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes as well as CD14+/CD80+ monocytes were analyzed by flow cytometry after PBMCs culture with PHA plus E. coli LPS. A significant decrease in the percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes was observed in CB compared to AB. In HKBA cultures, compared to E. coli LPS-cultures, there was a significant reduction of CD4+/CD25+ T-lymphocytes in all groups and CD14+/CD80+ in patients groups. We suggest that Brucella can modulate host immune response, leading to T-cell anergy and chronic infection.

  18. 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

  19. Death deflected: IL-15 inhibits TNF-alpha-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ralpha chain.

    Science.gov (United States)

    Bulfone-Paus, S; Bulanova, E; Pohl, T; Budagian, V; Durkop, H; Ruckert, R; Kunzendorf, U; Paus, R; Krause, H

    1999-09-01

    Interleukin-15 (IL-15) is a potent inhibitor of several apoptosis pathways. One prominent path toward apoptosis is the ligand-induced association of TNF receptor 1 (TNFR1) with death domain adaptor proteins. Studying if and how IL-15 blocks TNFR1-mediated apoptosis in a murine fibroblast cell line (L929), we show here that IL-15 blocks TNFR1-induced apoptosis via IL-15Ralpha chain signaling. The intracellular tail of IL-15Ralpha shows sequence homologies to the TRAF2 binding motifs of CD30 and CD40. Most important, binding of IL-15 to IL-15Ralpha successfully competes with the TNFR1 complex for TRAF2 binding, which may impede assembly of key adaptor proteins to the TNFR1 complex, and induces IkappaBalpha phosphorylation. Thus, IL-15Ralpha chain stimulation is a powerful deflector of cell death very early in the apoptosis signaling cascade, while TNF-alpha and IL-15 surface as major opponents in apoptosis control.

  20. Change of CD4+ CD25+ Regulatory T Cells in Patients with Gastric Cancer before and after Operation%胃癌患者手术前后CD4+CD25+调节性T细胞的变化

    Institute of Scientific and Technical Information of China (English)

    史学菲; 白平; 唐承薇; 王春晖

    2011-01-01

    目的 研究胃癌患者手术前、后调节性T细胞(Treg)及FoxP3表达的变化.方法 采用流式细胞术检测20例胃癌患者术前及其中15例接受了手术者术后1周(简称术后)以及15例因胃部不适接受胃镜检查的自愿者(正常对照组)外周血中Treg数量的变化,用RT-PCR法检测Treg的特异性分子标志物FoxP3的转录水平,同时用免疫组织化学法检测胃癌组织中FoxP3蛋白的表达情况.结果 胃癌患者术前外周血中CD4+T细胞中的CD4+ CD25+比例明显高于正常对照组[(19.39±5.58)%比(9.91±3.23)%,P<0.01],而术后CD4+ CD25+比例较术前明显下降[(13.50±5.93)%比(19.39±5.58)%,P<0.05].胃癌患者术前外周血中FoxP3转录水平明显高于正常对照组(0.86±0.03比0.64±0.02,P<0.01),而术后较术前明显下降(0.73±0.04比0.86±0.03,P<0.05),提示FoxP3转录水平与Treg变化一致.胃癌患者外周血中CD4+T细胞在单个核细胞中的比例与正常对照组相比明显下降(P<0.01),而手术前、后变化不明显.20例胃癌患者中13例胃癌癌细胞的细胞浆中有不同程度的FoxP3蛋白表达(强阳性2例,中阳性6例,弱阳性5例),7例胃癌患者的胃癌细胞中不表达.结论 Treg可能通过免疫抑制作用在胃癌的发生、发展中发挥作用,肿瘤组织本身可能是引起Treg变化的重要始动因素.%Objective To investigate the levels of regulatory T cells (Treg) and FoxP3 gene in patients with gastric cancer before and after operation. Methods Twenty patients with definite diagnosis of gastric cancer and 15 healthy volunteers were selected. The levels of Treg and T cell subsets in peripheral blood were determined by detecting of CD4 and CD25 with immune-fluorescence stain and flow cytometry, the expressions of FoxP3 mRNA in these Treg were detected by RT-PCR technique. The expression of FoxP3 protein in the gastric cancer tissue was measured by immunohistochemistry assay. Results The percentage of Treg cells in

  1. Changes of CD4+CD25+ regulatory T cells in sepsis patients and its relationship with prognosis%脓毒症患者CD4+CD25+调节性T细胞的变化及其与预后的关系

    Institute of Scientific and Technical Information of China (English)

    孙仁华; 李茜; 邱莲女

    2009-01-01

    Objective To evaluate the changes of peripheral blood CD4+CD25+ regulatory T cells and its prognostic value in sepsis patients.MethodThe percentage of CD4+CD25+/CD4+ T cells were measured by flow eytometry present in peripheral blood in 36 sepsis patients on day 1,3 and 5 and 15 healthy people (control group).The changes of CD4+CD25+ regulatory T cells were analyzed in survivors group and non-survivors group respectively.Results There were 19 survivors and 17 non-survivors in sepsis patients.The percentage of CD4+CD25+/CD4+ T cells in survivors group and non-survivors group on day 1 was significantly lower than that in eontrol group [(12.42± 3.26)%,(12.96± 3.00)% vs (16.97 ± 3.66)%,P<0.05].The percentage of CD4+CD25+/CD4+ T cells in survivors group and non-survivors group on day 3 were both signifieanfly higher than that on day 1 [(24.47±4.62)%vs (12.42±3.26)%,(26.61±3.85)%vs (12.96±3.00)%,P<0.05].The percentage of CD4+CD25+/CD4+ T cells in survivors group on day 5[(18.28±4.28)%]was significantly lower than that on day 3 (P<0.05),and the percentage of CD4+CD25+/CD4+ T cells in nonsurvivors group on day 5 were significantly higher than that on day 3(P<0.05).There was no significant difference in the percentage of CD4+CD25+/CD4+ T ceils between survivors group and non-survivors group on day 1,3 respeefively(P > 0.05),but the percentage of CD4+CD25+/CD4+ T cells in survivors group was significantly lower than that in non-survivors group on day 5 (P<0.05).Conclusions The CD4+CD25+ regulatory T cells in sepsis patients decreases following by increase after onset.The persistent increase suggests the emergence of immunoparalysis,which is followed by high monaliy,The CD4+CD25+ regulatory T cells are valuable in evaluation of immune state and prediction the prognosis in sepsis patients.%目的 评价脓毒症患者外周血中CD4+CD25+调节性T细胞的变化趋势及其与预后的相关性.方法 采用流式细胞仪检测36例脓

  2. Study of changes of CD4+CD25+Foxp3+ regulatory T cells of Peripheral Blood in prostate cancer patients and staging of tumor%前列腺癌患者外周血CD4+CD25+Foxp3+调节性T细胞的变化及与肿瘤分期的相关性

    Institute of Scientific and Technical Information of China (English)

    汪铁军; 谢中华; 郑元秀; 王珠美

    2012-01-01

    Abstract Objective To investigate the relationship between the changes of CD4+CD25+Foxp3+ regulatory T cells of peripheral blood in prostate cancer patients and the international staging of tumor. Methods The number of CD4+CD25+Foxp3+ regulatory T cell in peripheral blood of 43 patients with prostate cancer (staging of tumor: II 18, III 10 and IV 8) and 20 healthy examiners were detected by the flow cytometry. The relationship between the changes of CD4+CD25+Foxp3+ regulatory T cells and the staging of tumor was statistically analyzed. Results Compared with that of the healthy control group, the proportion and number of CD4+CD25+Foxp3+ regulatory T cells of peripheral blood in prostate cancer patients were all increased significantly (P0.05). The proportion and number of CD4+CD25+Foxp3+ regulatory T cells in the high-risk group were increased significantly than that in the low-risk group and average-risk group (P<0.01, P<0.05). The proportion and number of CD4+CD25+Foxp3+ regulatory T cells were positively correlated with the staging of tumor and risk level. Conclusion Higher proportion and number of CD4+CD25+Foxp3+ regulatory T cells are found in peripheral blood in prostate cancer patients , and they increase with the staging . The level of CD4+CD25+Foxp3+ regulatory T cells may be useful in evaluation of the patient's condition .%目的 观察前列腺癌(PCa)患者外周血单个核细胞CD4+CD25+Foxp3+调节性T细胞的变化及其与国际肿瘤淋巴结转移(TNM)分期的关系.方法 采用流式细胞术检测20例体检健康者(对照组)及43例PCa患者(患者组,临床TNM分期Ⅰ期7例、Ⅱ期18例、Ⅲ期10例、Ⅳ期8例)外周血单个核细胞CD4+CD25+Foxp3+调节性T细胞数目,并计算CD4+CD25+Foxp3+调节性T细胞占CD4+T淋巴细胞的百分比;分析CD4+CD25+Foxp3+调节性T细胞与肿瘤分期的相关性.结果 与正常对照组比,患者组外周血单核细胞CD4+CD25+Foxp3+Treg占CD4+T淋巴细胞的百分比及CD4+CD25+Foxp3

  3. 外用他克莫司对寻常型银屑病患者CD4+CD25+调节性T细胞的影响%Effect of tacrolimus onitment on CD4+ and CD25+Treg cells in patients with psoriasis vulgaris

    Institute of Scientific and Technical Information of China (English)

    杨晓梅; 何荣国

    2010-01-01

    Objective To explore the effect of tacrolimus onitment on the changes of CD4+ and CD25+ Treg cells in peripheral blood from patients with psoriasis vulgaris. Methods 48 patients with psoria-sis vulgaris were treated with a topical immunomodulator, tacrolimus ointment 0.1%, twice daily for 8 weeks.The proportion of CD4+ and CD25+ Treg cells population in total T cells were evaluated by flowing cytometry before and after treatment. PASI was measured in all the patients. Results After 8-week treatment, the response rates was 91.5%. Before treatment, in the active stage and resting stage of psoriasis vulgaris and healthy controls, the proportion of CD4+ and CD25+ Treg cells population in total T cells was (2.64 ± 0.86) %,(3.98 ± 0.96) %, and (8.46 ± 1.54) %, with a significant difference among the three groups (P<0.01). After treatment, the proportion of CD4+ and CD25+ Treg cells population was obviously increased, but still lower than that in the healthycontrols (P<0.O1). Conclusions CD4+ and CD25+ Treg cells are abnormal in patients with psoriasis vulgaris. Tacrolimus can treat psoriasis vulgaris by upregulating CD4+ and CD25+ Treg cells.%目的 探讨外用他克莫司对寻常型银屑病患者外周血CD4+CD25+调节性T细胞(CD4+CD25+Treg)的影响.方法 给予48例寻常型银屑病患者他克莫司软膏,每日2次外用,用药8周.治疗前和治疗后,用流式细胞仪检测患者外周血CD4+CD25+调节性T细胞的表达水平,并对患者进行PASI评分.结果 治疗8周后,总有效率为91.5%.治疗前,银屑病进行期、静止期患者及正常人外周血CD4+CD25+Treg与CD4+淋巴细胞的百分比为(2.64±0.86)%、(3.98±0.96)%、(8.46±1.54)%,三者比较,差异均有极显著性(P<0.01);治疗后,进行期和静止期患者外周CD4+CD25+Treg与CD4+淋巴细胞的百分比较治疗前均有明显升高(P<0.01),但仍低于正常人,三者比较,差异均有极显著性(P<0.01).结论 寻常型银屑病存在CD4+CD25+调节性T细

  4. 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...

  5. 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

  6. Human T cell priming assay: depletion of peripheral blood lymphocytes in CD25(+) cells improves the in vitro detection of weak allergen-specific T cells.

    Science.gov (United States)

    Vocanson, Marc; Achachi, Amine; Mutez, Virginie; Cluzel-Tailhardat, Magalie; Varlet, Béatrice Le; Rozières, Aurore; Fournier, Philippe; Nicolas, Jean-François

    2014-01-01

    To develop an in vitro assay that recapitulates the key event of allergic contact dermatitis (ACD), that is the priming of effector T cells by hapten-presenting dendritic cells, and then allows for the sensitive detection of chemical allergens represents a major challenge. Classical human T cell priming assays (hTCPA) that have been developed in the past, using hapten-loaded monocyte-derived dendritic cells (MDDCs) as antigen-presenting cells and peripheral blood lymphocytes (PBLs) as responding cells, were not efficient to prime T cells to common allergens with moderate/weak sensitizing properties. Recent progress in the understanding of the effector and regulatory mechanisms of ACD have shown that T cell priming requires efficient uptake of allergens by immunogenic DCs and that it is controlled by several subsets of regulatory cells including CD25(+) Tregs. We therefore analyzed various parameters involved in allergen-specific T cell activation in vitro and showed that priming of allergen-specific T cells is hampered by several subsets of immune cells comprising CD1a(neg) DCs, CD25(+) T cells, and CD56(+) regulatory cells.CD4(+)CD25(+)FoxP3(+) Tregs prevented the in vitro T cell priming to moderate/weak allergens, and depletion of human PBLs in CD25(+) cells significantly increased specific T cell proliferation and IFN-γ secretion. CD56(+) cells exerted an additional control of T cell priming since co-depletion of both CD56(+) and CD25(+) cells improved the magnitude of chemical-specific T cell activation. Finally, CD1a(low) MDDCs were able to inhibit T cell activation obtained by allergen-pulsed CD1a(high) MDDC. Moreover, we showed that uptake by DC of allergen-encapsulated nanoparticles significantly increased their activation status and their ability to prompt specific T cell activation. Hence, by combining the different strategies, i.e., depletion of CD25(+) and CD56(+) cells, use of CD1a(high) MDDC, and nanoparticle encapsulation of allergens, it was

  7. Evaluation of PLGA containing anti-CTLA4 inhibited endometriosis progression by regulating CD4+CD25+Treg cells in peritoneal fluid of mouse endometriosis model.

    Science.gov (United States)

    Liu, Qi; Ma, Pingchuan; Liu, Lanxia; Ma, Guilei; Ma, Jingjing; Liu, Xiaoxuan; Liu, Yijin; Lin, Wanjun; Zhu, Yingjun

    2017-01-01

    Our study investigated poly(lactic-co-glycolic acid) (PLGA) as protein delivery vehicles encapsulate CTLA-4-antibody (anti-CTLA-4) which is essential for CD4+CD25+Treg cells suppressive function exposing superior potential for inhibiting endometriosis progress in mouse model than single anti-CTLA-4. Anti-CTLA-4 loaded PLGA combined to ligands CTLA-4 in surface of CD4+CD25+Treg cells which distributed in peritoneal fluid of mouse endometriosis model. The particle size, zeta potential of the anti-CTLA-4 loaded nanoparticles was detected by dynamic light scattering. Morphology of nanoparticles was evaluated by transmission electron microscopy (TEM). Confocal laser scanning microscopy (CLSM) indicated distribution of anti-CTLA-4 with PLGA or without in peritoneal fluid. Cumulative anti-CTLA-4 release from nanoparticles was evaluated by Micro BCA assay. The percentage of CD4+CD25+Treg cells in peritoneal fluid was demonstrated by flow cytometer. In vitro experiment we co-culture ectopic endometrial cells (EEC) with isolated CD4+CD25+Treg cells in peritoneal fluid (PF), proliferation and invasion of ectopic endometrial cells (EEC) was measured by BrdU ELISA assay and Matrigel invasion assay. In comparison with anti-CTLA-4 without nanoparticles, the bioconjugates PLGA/anti-CTLA-4 were tolerated in peritoneal fluid with a controlled release of anti-CTLA-4 in 3, 7, 14days. Moreover, PLGA/anti-CTLA-4 had superior protective regulation ability to reduce level of CD4+CD25+Treg cells in peritoneal fluid. Most strikingly, in vitro experiment, PLGA/anti-CTLA-4 exhibited better ability in inhibiting proliferation and invasion of ectopic endometrial cells in co-culture system compared with anti-CTLA-4. Progressively, PLGA/anti-CTLA-4 had better suppressive activity to inhibited IL-10 and TGF-beta secreted by CD4+CD25+Treg cells which indicating that PLGA/anti-CTLA-4 suppressed cells proliferation and invasion through reduced IL-10 and TGF-beta production. Thus, PLGA/anti-CTLA-4 may

  8. CD4~+CD25~+调节性T细胞对巨噬细胞泡沫化的影响%CD4~+ CD25~+ regulatory T cells inhibit macrophage-derived foam cells formation by down-regulating scavenger receptor expression

    Institute of Scientific and Technical Information of China (English)

    林静; 李大主

    2010-01-01

    Objective To investigate whether and how regulatory T cells(Tr) affect macrophages foam-cell formation, and thereby investigate the mechanism of Tr in the development of atherosclerosis. Methods Tr were isolated from lymphocyte suspensions by magnetic cell sorting-column and analyzed by flow cytometry. Macrophages were cultured alone, with CD4~+ CD25~+ T, or CD4~+ CD25~- T cells in the pres-ence of oxLDL for 48 h to transform macrophages into foam cells. Oil red O staining and cellular lipid meas-urement were used to identify macrophage foam cell formation. Semi-quantitative PCR, quantitative real-time PCR and Western blot analysis were carried out to explore the mechanism of Tr-mediated suppression on macrophages foam cell formation. Results Foam cell formation, as identified by oil red O staining, was readily apparent in cells treated with CD4~+ CD25~- T cells and without T cells. After treatment with Tr, a marked decrease(13.9% ± 5.6% ) in foam cell count was observed, compared with untreated cells(13.9% ±5.6% vs 52.9% ± 10.4%, P<0.001 ) or CD4~+ CD25~- T-treated cells(13.9% ± 5.6% vs 53. 1% ± 17.2%, P<0.001 ), 52.9% ± 10.4% and 53.1% ± 17.2%, respectively (P<0.001). The similar effect of Tr was obtained when extracted oil red O and measured by a spectrophotometer. Cholesteryl ester ac-cumulation also used to quantify foam cell formation. Compared with untreated (no T) and CD4~+ CD25~- Tr-treated macrophage cells (CD25~-), the lipids accumulation in CD4~+ CD25~+ Tr-treated macrophage foam cells(CD25~+) was significantly reduced. Total cellular cholesterol and cellular cholesteryl ester was siginifi-cantly reduced in CD25~+ cultures relative to no T[TC(total cholesterol): 57.46 ± 17.92 vs 159.48 ± 16.38, P<0.01 ; CE(esterified cholesterol): 26.68 ± 8.88 vs 102.54 ± 16.67, P<0.001] or CD25~- (TC: 58.50±7.00 vs 150.55±25.11, P<0.01; CE: 26.68±8.88 vs96.90 ± 11.95, P<0.001) cul-tures. Moreover, PCR and Western blot analysis showed that the expression

  9. 急性冠脉综合征患者外周血 CD4+ CD25+ Foxp3+Treg细胞的表达%Peripheral blood CD4+CD25+Foxp3+Treg cells in patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    邓穗燕; 李琴; 林丽英; 黄俊

    2014-01-01

    目的::探讨急性冠脉综合征( ACS)患者外周血CD4+CD25+Foxp3+Treg细胞亚群的表达量及其与ACS的关系。方法:采用流式细胞仪( FCM)检测16例ACS患者( ACS组)、12例稳定性心绞痛患者( SA组)和20例健康志愿者( Control组)外周血CD4+CD25+Tre细胞和CD4+CD25+Foxp3+Treg细胞的百分含量;采用酶联免疫吸附试验( ELISA)检测3组研究对象外周血细胞因子TGF ̄β1和IL ̄10水平;并采用透射比浊法检测3组研究对象血浆超敏C ̄反应蛋白( hs ̄CRP )和血糖、血脂水平。结果:3组研究对象外周血CD4+CD25+Treg细胞百分含量差异无统计学意义( P>0.05);ACS组外周血CD4+CD25+Foxp3+Treg细胞水平和血浆TGF ̄β1、IL ̄10浓度较SA组和Control组均明显降低(P0.05)。结论:CD4+CD25+Foxp3+Treg细胞数量和/或功能的下降可能与ACS的发生和发展密切相关,Foxp3标记可能有助于进一步识别ACS相关的Treg细胞。%Objective:To analyze the expression level of CD4+CD25+Foxp3+regulatory T ( Treg) cell subset in peripheral blood of patients with acute coronary syndrome ( ACS) and its correlation with ACS. Methods:Flow cytometry ( FCM) was used to measure the percentage contents of CD4+CD25+ Treg cells and CD4+CD25+Foxp3+Treg cells in the peripheral blood from 16 ACS patients ( ACS group) , 12 patients with stable angina ( SA group) , and 20 healthy volunteers ( Control group) . The levels of peripheral blood cytokines TGF ̄β1 and IL ̄10 in the three groups were measured by enzyme ̄linked immunosorbent assay ( ELISA) . The levels of hypersensitive C ̄reactive protein ( hs ̄CRP ) , blood glucose and blood lipids were measured by transmission turbidimetry. Results:There was no statistical difference in the percentage content of peripheral blood CD4+CD25+Treg cells among the three groups ( P>0. 05 ) . The levels of peripheral CD4+ CD25+ Foxp3+ Treg cells and plasma concentrations of TGF ̄β1 and IL

  10. 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.

  11. 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

  12. Interleukin-12 (IL-12p70 promotes induction of highly potent Th1-like CD4+CD25+T regulatory cells that inhibit allograft rejection in unmodified recipients.

    Directory of Open Access Journals (Sweden)

    Nirupama Darshan Verma

    2014-05-01

    Full Text Available In rat models, CD4+CD25+T regulatory cells (Treg play a key role in the induction and maintenance of antigen specific transplant tolerance, especially in DA rats with PVG cardiac allografts(1, 2. We have previously described generation of alloantigen specific Treg (Ts1, by culture of naïve natural CD4+CD25+ Treg (nTreg with specific alloantigen and IL-2 for 4 days. These cells express mRNA for IFN-γ receptor (ifngr and suppress donor but not third party cardiac allograft rejection mediated by alloreactive CD4+T cells at ratios of We induced highly suppressive Th1-like Treg from naïve nTreg in 7 days by culture with alloantigen, first with rIL-2 then with rIL-12p70. These Th1-like Treg delayed specific-donor allograft rejection demonstrating therapeutic potential

  13. 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.

  14. 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.

  15. 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.

  16. Serum Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) in Children with Chronic Hepatitis C: Relation to Liver Fibrosis and Viremia.

    Science.gov (United States)

    Sira, Mostafa M; Behairy, Behairy E; Abd-Elaziz, Azza M; Abd Elnaby, Sameh A; Eltahan, Ehab E

    2014-01-01

    Liver fibrosis and viremia are determinant factors for the treatment policy and its outcome in chronic hepatitis C virus (HCV) infection. We aimed to investigate serum level of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and its relation to liver fibrosis and viremia in children with chronic HCV. ITIH4 was measured by ELISA in 33 treatment-naive children with proved chronic HCV and compared according to different clinical, laboratory and histopathological parameters. Liver histopathological changes were assessed using Ishak score and compared with aspartate transaminase-to-platelet ratio (APRI) and FIB-4 indices as simple noninvasive markers of fibrosis. ITIH4 was measured in a group of 30 age- and sex-matched healthy controls. ITIH4 was significantly higher in patients than in controls (54.2 ± 30.78 pg/mL versus 37.21 ± 5.39 pg/mL; P = 0.021). ITIH4, but not APRI or FIB-4, had a significant direct correlation with fibrosis stage (P = 0.015, 0.961, and 0.389, resp.), whereas, the negative correlation of ITIH4 with HCV viremia was of marginal significance (P = 0.071). In conclusion, ITIH4 significantly correlated with higher stages of fibrosis indicating a possible relation to liver fibrogenesis. The trend of higher ITIH4 with lower viremia points out a potential antiviral properties and further studies in this regard are worthwhile.

  17. Serum Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4 in Children with Chronic Hepatitis C: Relation to Liver Fibrosis and Viremia

    Directory of Open Access Journals (Sweden)

    Mostafa M. Sira

    2014-01-01

    Full Text Available Liver fibrosis and viremia are determinant factors for the treatment policy and its outcome in chronic hepatitis C virus (HCV infection. We aimed to investigate serum level of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4 and its relation to liver fibrosis and viremia in children with chronic HCV. ITIH4 was measured by ELISA in 33 treatment-naive children with proved chronic HCV and compared according to different clinical, laboratory and histopathological parameters. Liver histopathological changes were assessed using Ishak score and compared with aspartate transaminase-to-platelet ratio (APRI and FIB-4 indices as simple noninvasive markers of fibrosis. ITIH4 was measured in a group of 30 age- and sex-matched healthy controls. ITIH4 was significantly higher in patients than in controls (54.2±30.78 pg/mL versus 37.21±5.39 pg/mL; P=0.021. ITIH4, but not APRI or FIB-4, had a significant direct correlation with fibrosis stage (P=0.015, 0.961, and 0.389, resp., whereas, the negative correlation of ITIH4 with HCV viremia was of marginal significance (P=0.071. In conclusion, ITIH4 significantly correlated with higher stages of fibrosis indicating a possible relation to liver fibrogenesis. The trend of higher ITIH4 with lower viremia points out a potential antiviral properties and further studies in this regard are worthwhile.

  18. Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4+CD25+Foxp3+ T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model

    Directory of Open Access Journals (Sweden)

    Takaya Yamada

    2012-01-01

    Full Text Available Sublingual immunotherapy (SLIT has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs, but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN, which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

  19. 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

  20. 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

  1. 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

  2. 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

  3. An experimentally validated panel of subfamily-specific oligonucleotide primers (V alpha 1-w29/V beta 1-w24) for the study of human T cell receptor variable V gene segment usage by polymerase chain reaction.

    Science.gov (United States)

    Genevée, C; Diu, A; Nierat, J; Caignard, A; Dietrich, P Y; Ferradini, L; Roman-Roman, S; Triebel, F; Hercend, T

    1992-05-01

    We report here the characterization of a series of T cell receptor (TcR) V alpha or V beta subfamily-specific oligonucleotide primers. Criteria that have guided the design of each oligonucleotide include appropriate thermodynamic parameters as well as differential base-pairing scores with related and unrelated target sequences. The specificity of the oligonucleotides for each V alpha or V beta subfamily was tested by polymerase chain reaction (PCR) on both a series of TcR encoding plasmid DNA and clonal T cell populations. Unexpected cross-reactivities were observed with plasmid cDNA sequences corresponding to unrelated subfamily gene segments. This led to the synthesis of additional series of oligonucleotides to obtain a relevant panel. A series of V alpha 1-w29/V beta 1-w24 TcR subfamily-specific oligonucleotides was eventually selected which generates little, if any, cross-reactivity. The use of C alpha or C beta primers for the amplification of internal positive control templates (i.e. C beta for the V alpha series and C alpha for the V beta series) has been tested in PCR performed with cDNA derived from peripheral blood lymphocytes; it was shown not to alter the amplification of the V subfamily-specific DNA fragments. This panel of oligonucleotides will be helpful in the study of TcRV gene segment usage and, thus, may lead to a better characterization of T cell responses in physiological and pathological situations.

  4. 肺积方调节CD4+CD25+Treg细胞及T淋巴细胞增殖与抗Lewis肺癌移植鼠肿瘤生长作用研究%Effects of Feijifang on Levels of CD4+CD25+Treg and T Lymphocytes and Tumor Growth in Mice with Trans-planted Lewis Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    杨国良; 张学进; 胡丹丹

    2013-01-01

    Objective:To investigate the effect of Feijifang combined with chemotherapy on tumor growth and the levels of CD4+CD25+ regulatory T cells(Treg) and T lymphocytes in mice with transplanted Lewis lung cancer and the underlying mechanism of Feijifang modulating immune evasion. Methods:Sixty-four mice with transplanted Lewis lung cancer were randomly divided into control group,Feiji group,comprehensive treatment group(Feijifang combined with diamminedichloroplatinum),and diamminedichloroplatinum (DDP) group,16 mice in each. The proliferation of T lymphocytes in the spleen and thymus was detected by MTT method and the percentage of CD4+CD25+Treg was assessed by flow cytometry. The volume and weight of tumors were recorded and evaluated. Results:The volume and weight of tumors in the DDP,Feiji,and comprehensive treatment groups were less than those in the control group (P0.05). On day 10 and 21,the percentage of CD4+CD25+Treg was lower in the DDP,Feiji,and comprehensive treatment groups as compared with that in the control group (P0.05)。第10、21天DDP组、肺积方组、综合组荷瘤小鼠胸腺CD4+CD25+Treg细胞比例均较对照组降低(P<0.05);DDP组第21天胸腺CD4+CD25+Treg细胞比例较第10天明显升高(P<0.05);综合组脾脏CD4+CD25+Treg细胞比例较低,与肺积方组、DDP组比较差异有统计学意义(P<0.05)。结论:肺积方联合化疗具有抗Lewis肺癌移植小鼠肿瘤生长的作用,该作用可能与其下调CD4+CD25+Treg细胞含量相关。

  5. 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.

  6. 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

  7. Effects of pepper artemisia on CD4+CD25+ regulatory T cells in experimental autoimmune orchitis mice%椒蒿对自身免疫性睾丸炎小鼠CD4+CD25+调节性T细胞的影响

    Institute of Scientific and Technical Information of China (English)

    仵燕; 斯依提尼沙汗·吾满尔; 吴小川; 骆靖华; 玛衣拉·阿不拉克

    2013-01-01

    Objective To study the effects of volatile oil from pepper artemisia leaves on CD4+ CD25+ regulatory T cells in murine autoimmune orchitis mice. Methods Totally 80 male BALB/c mice were randomly divided into 4 groups (normal saline group, model group, olive oil group, and pepper artemisia group). After model making, each group received gavage three days before the surgery, and for 24 days after the surgery (saline group received only the gavage, but no operation). CD4+CD25 + regulatory T cells in the peripheral blood were detected by flow cytometry 3 and 9 weeks after the surgery. Results Three weeks after the surgery, the percentage of peripheral blood CD4+ CD25+ regulatory T cells in model group, olive oil group and pepper artemisia group was significantly lower than that in saline group (P0.05). Nine weeks after the operation, the percentage of peripheral blood CD4+CD25+ regulatory T cells was significantly lower in model group and olive oil group than in saline group (P0.05). Conclusion Pepper artemisia can increase the percentage of CD4+CD25+ regulatory T cells, which exert immunity-regulatory effects on autoimmune orchitis mice.%目的 研究椒蒿挥发油对自身免疫性睾丸炎小鼠CD4+ CD25+调节性T细胞的影响.方法 雄性BALB/c小鼠80只,随机分为4组(生理盐水组、模型组、橄榄油组、椒蒿组),采用睾丸内注射冰醋酸的方法造模,各组都在手术前3天开始灌胃,手术后继续灌胃,共连续灌胃24 d(盐水组只灌胃,不手术).分别于术后3周、9周取外周血,通过流式细胞仪对CD4+ CD25+调节性T细胞进行检测.结果 术后3周,模型组、橄榄油组、椒蒿组小鼠外周血CD4+ CD25+调节性T细胞百分比均低于生理盐水组,差异有统计学意义(P<0.05),而此3组之间差异无统计学意义(P>0.05).术后9周模型组与橄榄油组小鼠外周血CD4+ CD25+调节性T细胞百分比低于生理盐水组,差异有统计学意义(P<0.0S),椒蒿组与生理盐水组比

  8. 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

  9. 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

  10. Low circulating CD4(+) CD25(+) Foxp3(+) T regulatory cell levels predict miscarriage risk in newly pregnant women with a history of failure.

    Science.gov (United States)

    Winger, Edward E; Reed, Jane L

    2011-10-01

    PROBLEM  The purpose of this study was to determine whether quantification of peripheral blood Treg cell levels could be used as an indicator of miscarriage risk in newly pregnant women with a history of immunologic reproductive failure. METHOD OF STUDY  Fifty-four pregnant women with a history of immunologic infertility and/or pregnancy loss were retrospectively evaluated (mean age: 36.7 ± 4.9 years, 2.8 ± 2.5 previous miscarriages; 1.5 ± 1.9 previous IVF failures). Twenty-three of these women experienced another first trimester miscarriage, and 31 of these women continued their current pregnancies past 12 weeks ('pregnancy success'). The following immunologic parameters were assessed in the first trimester: NK cell 50:1 cytotoxicity, CD56(+)  16(+)  CD3(-) (NK), CD56(+)  CD3(+) (NKT), TNFα/IL-10, IFNγ/IL-10, CD4(+)  CD25(-) Foxp3(+) , total CD4(+)  Foxp3(+) (CD4(+ ) CD25(+)  Foxp3 plus CD25(- ) Foxp3(+) ), and CD4(+)  CD25(+)  Foxp3(+) levels. RESULTS  Patients with successful ongoing pregnancies experienced a mean (CD4(+)  CD25(+)  Foxp3(+) ) 'Treg' level of 0.72 ± 0.52%, while those that miscarried in the first trimester experienced a mean Treg level of 0.37 ± 0.29% (P = 0.005). Markers not significantly different between the loss and success groups were NK 50:1 cytotoxicity (P = 0.63), CD56(+)  16(+)  3(+) NK cells (P = 0.63), CD56(+)  3(+)   NKT (P = 0.30), TNFα(+) IL-10(+) (P = 0.13), IFNg(+) IL-10(+) (P = 0.63), and CD4(+)  25(-)  Foxp3(+) cells (P = 0.10), although total CD4(+)  Foxp3(+) levels remained significant (P = 0.02) and CD4(+)  25(+) Foxp3(+) showed the most significant difference (P = 0.005). Mean day of blood draw was 49.2 ± 36.1 days pregnant (median 39.0 days). In addition, patients with a low Treg level (0.7%) in the first trimester [44% (15/34) versus 80% (16/20); P = 0.01]. Of the 18 successful pregnancies with sequential Treg

  11. 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.

  12. 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

    sacrificed weekly from week 1 to 4. Clinical signs of colitis occurred approximately 2 weeks after reconstitution. Disease onset and severity based on histopathology correlated well with the colonic weight:length ratio, fecal consistency score, presence of occult blood in feces, and fecal IL-1beta content....... Purification of CD4+CD25- T cells is a simple procedure, and does not require flow-cytometric sorting. Fecal consistency score and colonic weight:length ratio are readily measurable and consistent disease parameters. This model is thus highly suitable for pharmacological testing of intervention strategies....

  13. 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...... 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...

  14. 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

    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....

  15. 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

  16. 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.

  17. 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.

  18. Study of Different Death Patterns of Huaman Peripheral Blood CD4+CD25+T Lymphocytes Induced by Anti-CD137 mAb%共刺激分子CD137单克隆抗体对CD4+CD25+T淋巴细胞死亡方式影响的研究

    Institute of Scientific and Technical Information of China (English)

    尹柯; 周文英; 邬伟明; 黄瑾

    2009-01-01

    目的:初步观察抗共刺激分子CD137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、胀亡现象的影响及其表面特征性标志物FOXp3的表达的变化.方法:采用密度梯度离心法及尼龙棉柱法分离健康志愿者外周血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、检测各分组(抗CD137单克隆抗体2 μg/ml组、IgGl同型抗体对照组)的细胞的自噬率、凋亡率、胀亡率及FOXp3的表达.结果:MACS可成功分离CD4+CD25+T淋巴细胞,纯度可达80.3%~89.5%;抗CD137单克隆抗体可促进人外周血CD4+CD25+T淋巴细胞自噬率及凋亡率增加;各组间的胀亡率改变及FOXp3表达差异无统计学意义.结论:抗CD137单克隆抗体可促进CD4+CD25+T淋巴细胞凋亡和自噬,其作用机制未发现与胀亡显著相关,而且不影响CD4+CD25+T细胞中Foxp3的表达.

  19. 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

  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. 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.

  2. 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

  3. 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.

  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. 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

  6. 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.

  7. Combinative application CD4+ CD25+ regulatory T cells test and irregular antibody screening in the diagnosis of invalid clinical transfusion%联合检测CD4+ CD25+调节性T细胞和血清不规则抗体在红细胞输注无效诊断的应用研究

    Institute of Scientific and Technical Information of China (English)

    李忱炜

    2016-01-01

    Objective To investigate whether the T cells (CD4+ CD25+) levels and the irregular antibodies screening cloud improve the diagnosis of invalid red blood cells transfusion.Methods Thirty-one patients with red blood cell invalid transfusion in the People's Hospital of Yubei District of Chongqing were selected.Flow cytometry was used to detect the changes of CD4+CD25+ regulatory T cells.Standard cells Ⅰ,Ⅱ,Ⅲ were used to screen on irregular antibodies in red blood cells (RBC).Results The rate of invalid RBC transfusion was 7.52% (31/412) in Yubei District.The incidence rate of medical diseases was 77.42% (24/31),much higher than surgical disease (22.58% (7/31,P =0.002),and the major departments were oncology department,hematological department and infectious department.The CD4+ CD25+ regulatory T cells were decrease from (22.18±1.58) % to (16.57±1.77) %(P=0.023).Conclusion Combin CD4+CD25+ regulatory T cells test and irregular antibody screening can help prevent and reduce the invalid transfusionof red blood cells.%目的 通过联合检测红细胞输注前后调节性T细胞(CD4+ CD25+)的变化和不规则抗体存在情况,探讨其是否有利于提高患者红细胞输注无效的检出率.方法 选取渝北区人民医院红细胞输注无效患者31例,采用流式细胞术检测输血前后CD4+ CD25+调节性T细胞变化,采用标准筛查细胞Ⅰ、Ⅱ、Ⅲ检测血清低效价、低亲和力不规则抗体.结果 渝北区红细胞输注无效发生率为7.52%(31/412),内科系统患者红细胞输注无效构成比为77.42%(24/31),远大于外科系统患者的22.58%(7/31) (P=0.002),红细胞输注无效发生以肿瘤科、血液内科、感染科为主;红细胞输注无效患者CD4+CD25+调节性T细胞表达由(22.18±1.58)%下降至(16.57±1.77)% (P=0.023).结论 联合检测CD4+ CD25+T细胞的变化和不规则抗体表达,有利于提高红细胞输注无效的检出率,预防和减少红细胞输注无效.

  8. Expression of the IL-7 receptor alpha-chain is down regulated on the surface of CD4 T-cells by the HIV-1 Tat protein.

    Directory of Open Access Journals (Sweden)

    Denny McLaughlin

    Full Text Available HIV infection elicits defects in CD4 T-cell homeostasis in both a quantitative and qualitative manner. Interleukin-7 (IL-7 is essential to T-cell homeostasis and several groups have shown reduced levels of the IL-7 receptor alpha-chain (CD127 on both CD4 and CD8 T-cells in viremic HIV+ patients. We have shown previously that soluble HIV Tat protein specifically down regulates cell surface expression of CD127 on human CD8 T-cells in a paracrine fashion. The effects of Tat on CD127 expression in CD4 T-cells has yet to be described. To explore this effect, CD4 T-cells were isolated from healthy individuals and expression levels of CD127 were examined on cells incubated in media alone or treated with Tat protein. We show here that, similar to CD8 T-cells, the HIV-1 Tat protein specifically down regulates CD127 on primary human CD4 T-cells and directs the receptor to the proteasome for degradation. Down regulation of CD127 in response to Tat was seen on both memory and naive CD4 T-cell subsets and was blocked using either heparin or anti-Tat antibodies. Tat did not induce apoptosis in cultured primary CD4 T-cells over 72 hours as determined by Annexin V and PI staining. Pre-incubation of CD4 T-cells with HIV-1 Tat protein did however reduce the ability of IL-7 to up regulate Bcl-2 expression. Similar to exogenous Tat, endogenously expressed HIV Tat protein also suppressed CD127 expression on primary CD4 T-cells. In view of the important role IL-7 plays in lymphocyte proliferation, homeostasis and survival, down regulation of CD127 by Tat likely plays a central role in immune dysregulation and CD4 T-cell decline. Understanding this effect could lead to new approaches to mitigate the CD4 T-cell loss evident in HIV infection.

  9. 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

  10. 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.

  11. The origin of thymic CD4+CD25+ regulatory T cells and their co-stimulatory requirements are determined after elimination of recirculating peripheral CD4+ cells.

    Science.gov (United States)

    Zhan, Yifan; Bourges, Dorothee; Dromey, James A; Harrison, Leonard C; Lew, Andrew M

    2007-04-01

    Studies on the thymic ontogeny of naturally arising CD4(+)CD25(+) regulatory T cells (TR cells) are complicated by the contamination of recirculating cells from the periphery (both activated CD4(+) T and TR cells). We investigated TR cells in anti-CD4 antibody transgenic (Tg) (GK) mice that continuously deplete peripheral CD4 T cells but not thymocytes so that the generation of thymic TR cells and their developmental requirement can be accurately assessed. We show that in the thymuses of mice that lack peripheral CD4(+) cells, TR cells were present but were fewer in number compared with wild-type (WT) mice. Therefore, we show that peripheral TR cells do re-enter the thymus, comprising 20% of TR cells in the normal thymus. TR cells from both WT and GK mice expressed Foxp3 and GITR, and suppressed the proliferation of CD25(-)CD4(+) T cells. Furthermore, the co-stimulation requirements for TR generation were evaluated in mice with or without peripheral CD4 cells. Splenic TR cells in CD40L(-/-) mice and CTLA4Ig Tg mice were fewer compared with WT mice. Mice deficient in both co-stimulatory pathways had further reduction in splenic TR cells. Unlike the periphery, the reduction in thymic TR cells was only seen for CD40L(-/-) but not for CTLA4Ig Tg mice. Therefore, we found that the co-stimulation requirements for the thymic development of TR cells differed from those for peripheral homeostasis.

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

    Science.gov (United States)

    Islas-Vazquez, Lorenzo; Prado-Garcia, Heriberto; Aguilar-Cazares, Dolores; Meneses-Flores, Manuel; Galicia-Velasco, Miriam; Romero-Garcia, Susana; Camacho-Mendoza, Catalina; Lopez-Gonzalez, Jose Sullivan

    2015-01-01

    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. PMID:26582240

  13. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation.

    Science.gov (United States)

    Read, S; Malmström, V; Powrie, F

    2000-07-17

    It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25(+)CD45RB(low)CD4(+)) as those that control autoimmunity. Previous studies have failed to identify how CD25(+) Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor beta. Strikingly, constitutive expression of CTLA-4 among CD4(+) cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.

  14. 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.

  15. The role of dendritic cells in the generation of CD4(+) CD25(HI) Foxp3(+) T cells induced by amino acid copolymers.

    Science.gov (United States)

    Kawamoto, Norio; Ohnishi, Hidenori; Kondo, Naomi; Strominger, Jack L

    2013-01-01

    The effects of the amino acid copolymers used in the therapy of experimental autoimmune encephalomyelitis, poly(Y,E,A,K)(n) (Copaxone(®)) and poly(Y,F,A,K)(n), on murine myeloid cells have been investigated. After administration of these copolymers to mice, increases in several splenic myeloid cell populations were observed, including CD11b(+) CD11c(+) dendritic cells. The latter were the major splenic cell type that secreted CCL22 (macrophage-derived chemokine) on stimulation with amino acid copolymers. CCL22 secretion was also stimulated from bone marrow-derived dendritic cells (BMDC) generated with GM-CSF in much larger amounts than from bone marrow-derived macrophages generated with M-CSF. Moreover, CCL22 secretion could also be obtained using BMDC generated from two different types of MHC II(-/-) mice, indicating that an innate immune receptor is involved. Finally, incubation of these BMDC or splenic dendritic cells with naive CD4(+) CD25(-) T cells resulted in formation of CD4(+) CD25(HI) Foxp3 T cells (~25% of which were Foxp3(+)). The number of these regulatory cells was doubled by pretreatment of BMDC with amino acid copolymers.

  16. Clinical Significance of CD4 + CD25 (High) CD127(Low/-) Regulatory T Cells Frequency in Peripheral Blood of Patients with Active Rheumatoid Arthritis%类风湿关节炎外周血CD4+CD25(high)CD127(low/-)T细胞表达的变化及意义

    Institute of Scientific and Technical Information of China (English)

    武加标; 任敏; 汤丽; 李雪飞; 顾巧英; 戚传平; 肖菁; 赵东宝

    2013-01-01

    目的 探讨类风湿关节炎(Rheumatoid arthritis,RA)活动期患者外周血细胞表面CD4+ CD25 (high) CD127(low/-)调节性T细胞数量的变化.方法 用流式细胞术检测32名RA患者,14名膝关节骨性关节炎(osteoarthrosis of knee,OA)患者和13名正常人外周血细胞CD4+ CD25 (high) CD127(low/-)调节性T细胞的百分比,并统计分析其数量变化与有关临床和实验室指标的相关性.结果 RA患者外周血CD4+ CD25 (high) CD127(low/-)调节性T细胞在CD4T细胞中的百分率(4.82±0.49)均显著低于OA组(6.54 ±0.45)和组对照(7.05±0.62) (P <0.05),且与RA活动指数DAS28呈负相关(P<0.05).结论 RA患者外周血CD4+ CD25(high)CD127(low/-)调节性T细胞数量显著降低,提示该细胞亚群可能在调节RA疾病活动中发挥重要作用,并且也可以作为监测RA疾病活动一个重要指标.

  17. Analysis of Epstein-Barr viral DNA load, EBV-LMP2 specific cytotoxic T-lymphocytes and levels of CD4+CD25+T cells in patients with nasopharyngeal carcinomas positive for IgA antibody to EBV viral capsid antigen

    Institute of Scientific and Technical Information of China (English)

    MO Wu-ning; TANG An-zhou; ZHOU Ling; HUANG Guang-wu; WANG Zhan; ZENG Yi

    2009-01-01

    Background Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignant diseases including nasopharyngeal carcinoma (NPC), which is a common cancer in Southeastem Asia. Previous studies showed that plasma levels of EBV-DNA might be a sensitive and reliable biomarker for the diagnosis, staging and evaluating of therapy for NPC. There are a few analyses of the levels of EBV-latent membrane protein 2 (LMP2)-specific cytotoxic T-lymphocytes (CTLs) in patients with NPC. This study was conducted to investigate the levels of EBV-LMP2-specific CTLs, EBV-DNA load and the level of CD4+CD25+T cells in such patients.Methods From February 2006 to April 2006, 62 patients with NPC, 40 healthy virus carders positive for EBV viral capsid antigen (EBV-IgA-VCA) and 40 controls were enrolled in the study. We used a highly sensitive ELISPOT assay,real-time polymerase chain reaction (PCR) and flow cytometry to measure the EBV-LMP2-specific CTL response, the EBV DNA load and the level of CD4+CD25+T cells, respectively.Results The EBV-LMP2-specific CTL responses of the samples from the control, healthy virus carders and patients with NPC were significantly different from the LMP2 epitopes, with the control and healthy virus carder samples displaying a stronger response in three cases. There were significant differences in EBV DNA load in serum between NPC and the healthy groups; patients with NPC at stages Ⅲ or Ⅳ had significantly higher viral loads compared with those at stages Ⅰ or Ⅱ. A significantly higher percentage of CD4+CD25+ T lymphocytes were detected in the patients, compared with healthy virus carriers and healthy controls. Moreover, patients with advanced stages of NPC (Ⅲ and Ⅲ) had significantly higher percentages than the patients with early stages (Ⅰ and Ⅱ).Conclusions Patients with NPC are frequently unable to establish or maintain sufficient immunosurveillance to control proliferating B cells harboring EBV and to destroy the tumor

  18. 宫颈疾病患者外周血CD4+CD25+C-D127-/low Treg细胞的检测及临床意义%Detection of the expression of CD4+CD25+CD127-/low Treg cells in peripheral blood in patients with cervix diseases and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    袁冬兰; 钱华

    2012-01-01

    目的 检测宫颈癌、宫颈上皮内瘤变患者外周血CD4+CD25+CD127-/low Treg细胞的表达,分析其临床意义.方法 荧光抗体CD127-FITC、CD4-PECY5、CD25-PE标记T细胞,流式细胞术测定50例宫颈癌患者和49例宫颈上皮内瘤变患者中CD4+CD25+CD127-/low Treg细胞的表达.结果 与正常对照组[n=33,(8.07±2.18)%]比较,宫颈癌组[n=50,(11.15±1.97)%]、宫颈上皮内瘤变组[n=49,(10.61±2.62)%]CD4+CD25+CD127-low均显著升高,两者比较差异有统计学意义(t=6.018,P<0.001;t=4.943,P<0.001);与宫颈上皮内瘤变Ⅰ级组[n=16,(8.96±0.65)%]比较,宫颈上皮内瘤变Ⅱ~Ⅲ级组[n=33,(11.54±2.72)%]显著升高,两者比较有差异统计学意义(t=4.114,P<0.001);与宫颈癌Ⅰ期组[n=20,(10.34±1.79)%]比较,官颈癌Ⅱ期组[n=30,(11.68±1.97)%]显著升高,两者比较差异有统计学意义(t=2.424,P<0.05).结论 外周血CD4+CD25+CD127-/low Treg细胞的表达升高可能在宫颈癌和宫颈上皮内瘤变发病的发生、发展过程中起一定作用.%Objective To detect the expression of CD4+CD25+CD127-flow Treg cells in peripheral blood in patients with cervix cancer and cervical intraepithelial neoplasia (CIN), and to explore its clinical significance. Methods T cells were marked with fluorescence antibody CD127-FITC, CD4-PECY5, CD25-PE. The levels of CD4+CD25+CD127-flow Treg cells were detected by flow cytometry in 50 patients with cervix cancer (group A), 49 patients with CIN (group B), and 33 healthy individuals (the control group). Results Compared with the control group [(8.07±2.18)%], the levels of CD4+CD25+CD127-flow Treg cells in group A [(11.15±1.97)%] and group B [(10.61±2.62)%] were significantly higher (t=6.018,P<0.001;t=4.943 ,P<0.001). The level of CD4+CD25+CD127-flow Treg cells in patients with CIN of grade II ~ III [n=33, (11.54±2.72)%] was significantly higher than that in patients with CIN of grade I [n=16, (8.96±0.65)%], with t=4.114 and P<0

  19. 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

  20. 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.

  1. Depressive effect of cigarette smoke extracts on dendritic cells inducing differentiation of CD4+T cells into CD4+CD25+Foxp3+ Tregs%香烟烟雾提取物抑制树突状细胞诱导CD4+T细胞分化为CD4+CD25+Foxp3+调节性T细胞

    Institute of Scientific and Technical Information of China (English)

    梁毅; 周广; 张龙举; 刘积锋; 钟小宁

    2016-01-01

    目的 探讨香烟烟雾提取物(CSE)暴露及抑制CD40-CD40L路径对小鼠髓源性树突状细胞(BMDC)诱导CD4+T细胞分化为CD4+ CD25+ Foxp3+调节性T细胞(Treg)的影响.方法 使用40 ng/mL重组小鼠粒细胞-巨噬细胞集落刺激因子(rmGM-CSF)和10 ng/mL重组小鼠白细胞介素4(rmIL-4)联合诱导无特定病原体级健康雄性BALB/c小鼠骨髓来源的单个核细胞分化为树突状细胞(DC),流式细胞术检测小鼠BMDC表面CD40分子的表达,再采用免疫磁珠分选的方法从BALB/c小鼠脾脏细胞分离出CD4+T细胞.将所培养出的小鼠BMDC与正常对照组小鼠脾脏细胞分选的CD4+T细胞共培养,加入CSE及拮抗性CD40抗体,作用24h;流式细胞术观察各组细胞CD4+ CD25+ Foxp3+ Treg的变化,液相芯片技术检测细胞上清液白细胞介素10(IL-10)、IL-6的水平.结果 BMDC与CD4+T淋巴细胞共培养可以促进CD4+ CD25+ Foxp3+ Treg分化,经CSE刺激后,流式细胞术检测显示小鼠BMDC与CD4+T细胞共培养后分化的CD4+ CD25+ Foxp3+ Treg数量降低,细胞上清液IL-10降低、IL-6的水平升高;而加入拮抗性CD40抗体细胞共培养组CD4+ CD25+ Foxp3+ Treg增加,液相芯片检测细胞上清液IL-10上升、IL-6的水平下降.结论 CSE减少CD4+ CD25+ Foxp3+ Treg数量,体外使用拮抗性抗CD40抗体阻断CD40-CD40L通路可以促进CD4+T细胞分化为CD4+ CD25+ Foxp3+ Treg.

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

    Directory of Open Access Journals (Sweden)

    Uchiyama Masateru

    2012-03-01

    Full Text Available Abstract 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

  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. 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

  5. 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.

  6. An increase in CD3+CD4+CD25+ regulatory T cells after administration of umbilical cord-derived mesenchymal stem cells during sepsis.

    Directory of Open Access Journals (Sweden)

    Yu-Hua Chao

    Full Text Available Sepsis remains an important cause of death worldwide, and vigorous immune responses during sepsis could be beneficial for bacterial clearance but at the price of collateral damage to self tissues. Mesenchymal stem cells (MSCs have been found to modulate the immune system and attenuate sepsis. In the present study, MSCs derived from bone marrow and umbilical cord were used and compared. With a cecal ligation and puncture (CLP model, the mechanisms of MSC-mediated immunoregulation during sepsis were studied by determining the changes of circulating inflammation-associated cytokine profiles and peripheral blood mononuclear cells 18 hours after CLP-induced sepsis. In vitro, bone marrow-derived MSCs (BMMSCs and umbilical cord-derived MSCs (UCMSCs showed a similar morphology and surface marker expression. UCMSCs had stronger potential for osteogenesis but lower for adipogenesis than BMMSCs. Compared with rats receiving PBS only after CLP, the percentage of circulating CD3+CD4+CD25+ regulatory T (Treg cells and the ratio of Treg cells/T cells were elevated significantly in rats receiving MSCs. Further experiment regarding Treg cell function demonstrated that the immunosuppressive capacity of Treg cells from rats with CLP-induced sepsis was decreased, but could be restored by administration of MSCs. Compared with rats receiving PBS only after CLP, serum levels of interleukin-6 and tumor necrosis factor-α were significantly lower in rats receiving MSCs after CLP. There were no differences between BMMSCs and UCMSCs. In summary, this work provides the first in vivo evidence that administering BMMSCs or UCMSCs to rats with CLP-induced sepsis could increase circulating CD3+CD4+CD25+ Treg cells and Treg cells/T cells ratio, enhance Treg cell suppressive function, and decrease serum levels of interleukin-6 and tumor necrosis factor-α, suggesting the immunomodulatory association of Treg cells and MSCs during sepsis.

  7. 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.

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

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    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.

  9. 脉冲高答量血液滤过对脓毒症患者CD4+CD25+调节性T细胞的影响%Effect of pulse high volume hemofiltration on CD4+CD25+ Treg cells in patients with sepsis

    Institute of Scientific and Technical Information of China (English)

    邵敏; 刘宝; 王锦权; 陶晓根; 周树生; 金魁; 张翠萍

    2011-01-01

    目的:探讨脓毒症患者CD4+CD25+调节性T细胞(Treg)的水平和意义以及脉冲高容量血液滤过(PHVHF)对它们的影响.方法:将2008年1月~2010年11月在安徽省立医院ICU住院的脓毒症患者40例按照疾病严重程度分为3组:脓毒症组14例,严重脓毒症组15例,脓毒症休克组11例.其中行PHVHF患者25例.40例脓毒症患者在入选当天和d5行流式细胞术检测血中CD4+CD25+Treg细胞的比例和CD3+、CD4+、CD8+和CD4+/CD8+水平.同时选取20例健康人为对照组.结果:健康对照组CD4+CD25+Treg细胞表达率为(0.39±0.23%);脓毒症组为(1.72±0.59%);严重脓毒症组(2.72±0.22%);脓毒性休克组(3.55±0.51%),后3组间两两比较有显著性差异(均P<0.05).脓毒症组CD3+、CD4+和CD4+/CD8+较正常对照组显著升高(P<0.05).严重脓毒症组和脓毒症休克患者CD3+、CD4+、CD4+/CD8+较正常对照组显著降低(均P<0.05).与死亡组比较,生存组PHVHF能更有效地降低CD4+CD25+Treg细胞的异常表达(P<0.05),上调CD3+、CD4+、CD8+和CD4+/CD8+水平.结论:CD4+CD25+Treg细胞在脓毒症的免疫发病机制中可能起着重要作用,随病情加重,免疫抑制加强.PHVHF可调整脓毒症患者T细胞亚群比例,改善其免疫抑制状态,可作为脓毒症免疫调节治疗的手段之一.%Objective:To study the level and significance of CD4+CD25+ Treg cells and CD3+,CD4+,CD8+ cells in peripheral blood of patients with sepsis and evaluate the effects of pulse high volume hemofiltration (PHVHF)on them. Methods:Forty patients with sepsis in ICU of Anhui Provicial Hospital were studied from January 2008 to November 2010.Patients were divided into three groups:sepsis group (n=14),severe sepsis group (n=15)and septic shock group (n=11).The expressions of CD4+CD25+ Treg cells and CD3+,CD4+,CD8+cells of 40 patients on the day 1 and day 5 were detected by flow cytometry and were compared.Twenty five patients receiving PHVHF were divided into two groups:death group (n=7

  10. 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

  11. 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.

  12. 松果体褪黑素对大鼠胸腺CD4~+CD25~+调节性T细胞发育及其相关基因Foxp3 的影响%Effect of pineal gland and melatonin on CD4~+CD25~+Treg cells development and Foxp3 expression of rat thymus

    Institute of Scientific and Technical Information of China (English)

    林晋; 郑琳; 黄云梅; 刘卉; 魏建恩; 周瑞祥

    2010-01-01

    目的 研究松果体摘除及补充褪黑素对大鼠胸腺CD4~+CD25~+ 调节性T 细胞(Treg 细胞)产生、输出及其相关基因叉状头/翅膀状螺旋转录子(Foxp3)表达的影响.方法 选用雄性清洁级SD 大鼠120只,分为正常组、假手术组、松果体摘除组、松果体摘除+褪黑素低剂量组[腹腔注射7.5mg/(kg.d)]和松果体摘除+褪黑素高剂量组[腹腔注射15mg/(kg.d)],术后4、8周取材.应用流式细胞检测技术、RT-PCR法及免疫组织化学染色法观察并分析松果体摘除及补充外源性褪黑素后胸腺及外周血CD4、CD25双阳性细胞数量及胸腺Foxp3表达的变化.结果 松果体摘除术后无论4周或者8周胸腺CD4~+CD25~+Treg 细胞数量均无明显变化,补充褪黑素后双阳性细胞数量呈时间、剂量依赖性明显增加;松果体摘除术后4周外周血CD4~+CD25~+Treg 细胞数量明显增加,但补充褪黑素后恢复正常,而术后8周各组之间无显著性差异;半定量RT-PCR 及免疫组织化学结果显示,松果体摘除后4周大鼠胸腺Foxp3 表达水平明显升高,补充高低两种剂量褪黑素后均有所下降并达到正常水平,而松果体摘除后8周各组之间Foxp3的表达无明显差异.结论 松果体摘除对胸腺CD4~+CD25~+Treg 细胞的产生无明显影响,但导致大鼠胸腺Foxp3 的转录和翻译明显增加,胸腺CD4~+CD25~+ Treg 细胞的输出增加,而补充外源性褪黑素后能逆转上述异常,长时间作用则其影响逐渐消失.

  13. 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.

  14. CD25+Foxp3+调节性T细胞和Th17细胞在口腔白斑组织中的表达%Expression of CD25+ Foxp3+ Regulatory T Cells and Th17 Cells in Oral Leukoplakia.

    Institute of Scientific and Technical Information of China (English)

    白杨; 王文梅; 王翔; 黄晓峰; 蒋文晖; 刘雅菁

    2011-01-01

    Objective: To investigate the role of Treg and Th17 during the development and progression of the premalignant lesions. Methods: We compared CD25/Foxp3 and IL—17 expression detected by immunohistochemical staining in 42 oral leukoplakia (with or without dysplasia), and compared with 10 normal oral mucosa and 13 oral squamous cell carcinoma. Results: There was increasing trend of expression of CD25+ Foxp3+ Treg cells between the cases of normal oral mucosa , oral leukoplakia with hyperplasia epithelium, oral leukoplakia with dysplasia epithelium and OSCC (P<0. 05). (They were numerated as 2.5±0. 65, 5. 22±1.19, 31.4±16.8 and 42.8±12.67 per high magnification field, respectively). Further, expression of CD25+ Foxp3+ Treg cells was higher in severe dysplasia OLK than in mild/moderate dysplasia OLK. In addition, there was increasing trend of IL— 17 expression which was found between the four groups of normal oral mucosa, oral leukoplakia with hyperplasia epithelium, oral leukoplakia with dysplasia epithelium and OSCC, but no statistical significances. Positive correlation was shown between the density of the subset of co—expression of CD25+ and Foxp3 + T cells and expression of IL—17 (r = 0.318, P<0.05). Conclusion: In assistance with Th17 Cells, Treg cells has played a certain role in the development of oral cancer.%目的:通过观察CD25+Foxp3+和IL-17阳性细胞在口腔黏膜白斑(oral leukoplakia,OLK)和口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)组织中的表达情况,探讨Treg细胞和Th17细胞在口腔癌发生发展过程中的变化.方法:采用免疫组织化学方法检测CD25+Foxp3+、IL-17阳性细胞在10例单纯增生性白斑、32例异常增生性白斑、13例OSCC和10例正常口腔黏膜中的变化情况.结果:正常口腔黏膜组、单纯增生性白斑组、异常增生性白斑组和OSCC组CD25+Foxp3+Treg细胞数量逐渐增高(P<0.05),依次为(2.5±0.65)、(5.22±1.19)、(31.4±16.8)和(42.8±12.67)

  15. Alpha Thalassemia

    Science.gov (United States)

    Alpha Thalassemia Physicians often mistake alpha thalassemia trait for iron deficiency anemia and incorrectly prescribe iron supplements that have no effect 1 on the anemia. αα αα Normal alpha ...

  16. 不同分期前列腺癌患者外周血CD4+CD25+Foxp3+调节性T细胞的变化及与胰岛素抵抗的相关性%Changes of CD4+ CD25+ Foxp3+ regulatory T cells in the peripheral blood and their correlation with insulin resistance in different stages of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    章步文; 黎钢; 叶津津; 李峥嵘

    2015-01-01

    目的:观察不同分期前列腺癌患者外周血单个核细胞CD4+ CD25+ Foxp3+调节性T细胞的变化及与胰岛素抵抗的关系. 方法:采用流式细胞术检测62例前列腺癌患者(患者组,临床TNM分期Ⅰ期5例、Ⅱ期16例、Ⅲ期21例、Ⅳ期20例)外周血单个核细胞(PBMC)中CD4+ CD25+ Foxp3+调节性T细胞数目,计算CD4+CD25+ Foxp3+调节性T细胞占CD4+T淋巴细胞的百分率;并检测其空腹胰岛素及空腹血糖水平,计算胰岛素抵抗指数(HOMA-IR);采用ELISA法测定外周血胰岛素样生长因子1(IGF-1)水平,分析CD4+ CD25+ Foxp3+调节性T细胞与胰岛素抵抗的相关性,并与42例健康体检者进行对照. 结果:与健康对照组相比,前列腺癌患者HOMA-IR明显升高(6.68±1.66vs3.68±1.42),IGF-1水平明显下降[(96.39 ±21.21) ng/ml vs(164.56 ±30.58) ng/ml],PBMC CD4+ CD25+ Foxp3+ Treg占CD4+T淋巴细胞的百分率[(13.88±0.96)%vs(5.33 ±0.65)%]及CD4+CD25+ Foxp3+ Treg绝对值[(3.55±0.29)×107vs(1.99 ±0.78)× 107]明显升高(P<0.05,P<0.01).患者PBMCCD4+ CD25+ Foxp3+ Treg占CD4+T淋巴细胞的百分率及CD4+ CD25+ Foxp3+ Treg绝对数、HOMA-IR均随TNM分期逐渐加重而增加,IGF-1逐渐下降;相关性分析表明:CD4+ CD25+ Foxp3+ Treg/CD4+T及CD4+ CD25+ Foxp3+ Treg绝对数均与HOMA-IR呈明显正相关(r分别为0.689、0.722,P<0.01),与IGF-1呈明显负相关(r分别为-0.896、-0.747,P<0.01). 结论:前列腺癌患者存在不同程度的胰岛素抵抗,且随着疾病程度的加重,外周血CD4+CD25+ Foxp3+调节性T细胞数目和比例及胰岛素抵抗逐渐加重;CD4+ CD25+ Foxp3+调节性T细胞可能通过调节胰岛素抵抗参与其形成和发展.

  17. 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.

  18. 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...

  19. 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

  20. Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels.

    Science.gov (United States)

    Barceló-Coblijn, Gwendolyn; Murphy, Eric J

    2009-11-01

    There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n-3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n-3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n-3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes beta-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n-3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n-3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n-3 levels.

  1. 慢性非细菌性前列腺炎/慢性骨盆疼痛综合征患者外周血CD4+CD25+T调节细胞功能检测及意义%TGF-β1The role of CD4+CD25+ regulatory T cells in the pathogenesis of chronic abacterial prostatitis/ chronic pelvic pain syndrome

    Institute of Scientific and Technical Information of China (English)

    王少刚; 白剑; 席启林; 胡东亮; 刘继红; 叶章群

    2008-01-01

    Objective To explore the role of CD4+CD25+ regulatory T cells in the pathogenesis of chronic abacterial prostatitis/chronic pelvic pain syndrome (CAP/CPPS). Methods Peripheral blood samples were collected from 45 CAP/CPPS patients and 18 healthy age-matched male persons. Peripheral blood mononuclear cells (PBMCs) were isolated. The percentages of CD4+CD25+ and CD4+ CD25high regulatory T cells were detected by flow cytometry. PCR was used to examine the mRNA expression of Foxp3, a transcription factor expressed in the CD4+ CD25+ cells. ELISA was used to examine the plasma level of tumor growth factor (TGF)-β1. Results There were no significant differences in the percentages of peripheral blood CD4+ CD25+ and CD4+ CD25highT cells between the CAP/CPPS patients and normal control group(both P>0.05). The Foxp3 mRNA in the PBMCs of the CAP/CPPS ⅢA and CAP/CPPS ⅢB patients were (0.69±0. 23) and (0.44±0.18) respectively, both significantly lower than that of the control group [(1.37±0.19), P 0.05);CAP/CPPSⅢA、ⅢB组患者外周血单个核细胞(PBMC)中Foxp3mRNA表达水平[(0.69±0.23)、(0.44±0.18)]较对照组(1.37±0.19)明显降低(P=0.035,P=0.014);CAP/CPPSⅢA、ⅢB组患者血清中TGF-β1水平[(18.09±10.45)pg/ml、(14.06±6.22)pg/ml]较对照组[(27.01±13.29)pg/ml]降低(P=0.041,P=0.024).结论 外周血CD44CD25+调节性T细胞数量与CAP/CPPS的发病无明显关联,CD4+CD25+调节性T细胞功能障碍可能参与CAP/CPPS发病机制;Foxp3基因与TGF-β1在CAP/CPPS的发病过程中起重要作用.

  2. T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states*

    Science.gov (United States)

    Parente, José Napoleão Tavares; Talhari, Carolina; Schettini, Antônio Pedro Mendes; Massone, Cesare

    2015-01-01

    BACKGROUND Leprosy is characterized histologically by a spectrum of different granulomatous skin lesions, reflecting patients' immune responses to Mycobacterium leprae. Although CD4+CD25+ FoxP3+ T regulatory cells are pivotal in the immuneregulation, presence, frequency, and distribution of Tregs in leprosy, its reactional states have been investigated in few studies. OBJECTIVES This study aimed to verify the frequency and distribution of regulatory T cells in different clinical forms and reactional states of leprosy. METHODS We performed an immunohistochemical study on 96 leprosy cases [Indeterminate (I): 9 patients; tuberculoid tuberculoid: 13 patients; borderline tuberculoid: 26 patients; borderline borderline: 3 patients; borderline lepromatous: 8 patients; lepromatous lepromatous: 27 patients; reversal reaction: 8 patients; and erythema nodosum leprosum: 2 patients]. RESULTS FoxP3-positive cells were present in 100% of the cases with an average density of 2.82% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was a statistically significant increment of FoxP3 expression in patients with leprosy reversal reactions when compared with patients presenting with type I leprosy (P= 0.0228); borderline tuberculoid leprosy (P = 0.0351) and lepromatous leprosy (P = 0.0344). CONCLUSIONS These findings suggest that Tregs play a relevant role in the etiopathogenesis of leprosy, mainly in type I leprosy reaction. PMID:25672298

  3. Galectin-9 ameliorates Con A-induced hepatitis by inducing CD4(+CD25(low/int effector T-Cell apoptosis and increasing regulatory T cell number.

    Directory of Open Access Journals (Sweden)

    Kun Lv

    Full Text Available 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(+CD25(low/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.

  4. The presence of B7-H4+ macrophages and CD25+CD4+ and FOXP3+ regulatory T cells in the microenvironment of nasal polyps - a preliminary report.

    Directory of Open Access Journals (Sweden)

    P Strek

    2011-04-01

    Full Text Available The nasal polyp (NP seems to represent the end-stage of longstanding inflammation in patients with chronic rhinosinusitis. The aim of our study has been to evaluate the presence of two regulatory cell populations in the microenvironment of NP: CD4+CD25high Foxp3+ (Treg cells and B7-H4-expressing macrophages. Treg cells are actively able to inhibit T lymphocytes, while the population of B7-H4-expressing macrophages has recently been described as characterized by a regulatory function similar to that of Treg cells. For our study, we evaluated 14 NP tissue samples. The samples were divided into two main groups, eosinophilic (NP and lymphocytic (NP, according to the predominant type of immune cell infiltration. The presence of Treg cells and B7-H4 positive macrophages in the samples was analyzed by FACS. Treg cells and B7-H4-expressing macrophages were identified in all the examined nasal polyps. The percentages of both Treg cells and of B7H4 positive cells found in the eosinophilic nasal polyps were higher than those found in the lymphocytic nasal polyps. Treg cells and B7H4+ macrophage subpopulations were present in the NP microenvironment and the alterations in their percentages were related to a distinct pattern of immune cell infiltration.

  5. Partial depletion of CD4(+)CD25(+)Foxp3(+) T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice.

    Science.gov (United States)

    Morampudi, Vijay; De Craeye, Stephane; Le Moine, Alain; Detienne, Sophie; Braun, M Y; D'Souza, Sushila

    2011-04-01

    CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells, are known to regulate responses to infectious agents. Here we compared disease progression in BALB/c and C57BL/6(B6) mice infected perorally with Toxoplasma gondii for 7 days and examined the affect of partial depletion of Treg cells in these mice. BALB/c mice were seen to be resistant to peroral infection whereas B6 mice were susceptible in terms of mortality. Although the depletion of Treg cells before infection had no effect on the survival of B6 or BALB/c mice, it resulted in increased parasite burdens in BALB/c mice, especially in the lamina propria, but not in B6 mice. Pro-inflammatory cytokines were also increased in Treg cells depleted BALB/c mice as compared to B6 mice. In addition Treg cell depleted BALB/c mice displayed increased ileal histopathology compared to their non-treated counterparts. These findings provide evidence for the contribution of Treg cells, in the resistance of BALB/c mice against peroral T. gondii infection.

  6. 4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression.

    Directory of Open Access Journals (Sweden)

    Hampartsoum B Barsoumian

    Full Text Available Costimulation with the recombinant SA-4-1BBL agonist of 4-1BB receptor on conventional CD4+ T cells (Tconvs overcomes the suppression mediated by naturally occurring CD4+CD25+FoxP3+ T regulatory cells (Tregs. The mechanistic basis of this observation has remained largely unknown. Herein we show that Tconvs, but not Tregs, are the direct target of SA-4-1BBL-mediated evasion of Treg suppression. IL-2 produced by Tconvs in response to 4-1BB signaling is both necessary and sufficient for overcoming Treg suppression. Supernatant from Tconvs stimulated with SA-4-1BBL contains high levels of IL-2 and overcomes Treg suppression in ex vivo Tconv:Treg cocultures. Removal of IL-2 from such supernatant restores Treg suppression and repletion of Tconv:Treg cocultures with exogenous recombinant IL-2 overcomes suppression. This study establishes 4-1BB signaling as a key circuit that regulates physical and functional equilibrium between Tregs and Tconvs with important implications for immunotherapy for indications where a fine balance between Tregs and Teffs plays a decisive role.

  7. 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

  8. 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.

  9. 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.

  10. Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25 T cells.

    Science.gov (United States)

    Dominitzki, Sabine; Fantini, Massimo C; Neufert, Clemens; Nikolaev, Alexei; Galle, Peter R; Scheller, Jürgen; Monteleone, Giovanni; Rose-John, Stefan; Neurath, Markus F; Becker, Christoph

    2007-08-15

    Chronic inflammatory diseases may develop when regulatory T cells (Tregs) fail to control the balance between tolerance and immunity. Alternatively, activated immune cells might prevent the induction or activation of Tregs in such diseases. In this study, we demonstrate that trans-signaling into T cells via the soluble IL-6 receptor completely abrogates the de novo induction of adaptive Tregs. Mechanistically, IL-6 trans-signaling augmented the expression of the TGF-beta signaling inhibitor SMAD7. Consequently, SMAD7 overexpression in T cells using newly created transgenic mice rendered CD4(+)CD25(-) T cells resistant to the induction of FoxP3. Finally, IL-6 trans-signaling inhibited Treg-mediated suppression in a murine model of colitis. In summary, IL-6 trans-signaling into T cells emerges as a key pathway for blockade of the development of adaptive Tregs and thus may play a pivotal role in shifting the balance between effector and regulatory T cell numbers in chronic inflammatory and autoimmune diseases.

  11. 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.

  12. Increase in circulating CD4⁺CD25⁺Foxp3⁺ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

    DEFF Research Database (Denmark)

    Riley, Caroline Hasselbalch; Jensen, Morten Krogh; Brimnes, Marie Klinge;

    2011-01-01

    blood have been reported in both hematologic and solid cancers. We have analyzed the number, phenotype, and function of circulating CD4(+)CD25(+)Foxp3(+) T cells in patients with chronic myeloproliferative neoplasms. Surprisingly, we found a marked expansion of this subset of lymphocytes in patients...

  13. 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

  14. Effect of Oxymatrine on CD4+CD25+ regulatory T cells and lymphocyte proliferation%氧化苦参碱对CD4+CD25+调节性T细胞(Tr)和淋巴细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    李建国; 伍斌; 谢红付; 张江林; 易梅; 李吉

    2008-01-01

    目的 通过分析氧化苦参碱(oxymatrine,OMT)各剂量组对小鼠外周血调节性T细胞(regulatory Tcells,Tr细胞)数量的影响,同时检测OMT对刀豆蛋白A(ConA)刺激的小鼠淋巴结T细胞增殖的影响.探讨OMT治疗ACD的免疫学作用机制.以期为临床用OMT治疗变态反应性疾病提供更深入的理论和实验依据.方法 建立DNFB诱发的小鼠ACD模型.以不同荆量的OMT、PBS、氢化可的松(HCT)进行腹腔注射(ip),在实验进程的第1、7、14、21和28天小鼠尾静脉采血,抗-CD3、抗-CD4、抗-CD25单抗进行三色免疫荧光标记,流式细胞术检测各组CD4+CD25+T细胞数量.利用羧基荧光素乙酰乙酸(CFDA-SE)染色,流式细胞术检测OMT对小鼠淋巴结T细胞增殖的影响.实验数据以SPSS 10.0以及CELLQuest软件进行处理.结果 体外实验证明,在500、125和31μg/mL组的OMT对小鼠淋巴结T细胞增殖呈剂量依赖性抑制,而在16、8、4和2μg/mL组的OMT对小鼠淋巴结T细胞增殖起促进作用,但其剂量依赖关系不明显.腹腔注射OMT能明显提高小鼠外周血中CD4+CD25+T细胞的数量,与HCT组比较(P<0.01),与PBS组比较(P<0.01).结论 OMT对小鼠淋巴结T细胞的增殖呈双向作用;腹腔注射OMT能明显提高小鼠外周血中CD4+CD25+T细胞的数量;即OMT对免疫系统的影响呈双向作用,OMT是一种双向免疫调节剂.%[Objective]To analyse Oxymatrine's(OMT)effects on the quantity of mouse's regulatory T cells(Tr cells)in the peripheral blood and mouse lymphocyte proliferation stimulated by con A,probe into the immunological mechanism that OMT treats allergic contact dermatitis(ACD).[Methods]Building up an ACD mouse medel stimulated by Dinitrofluorobenzene(DNFB),taking intraperitoneal injection (IP)by different dosage8 of OMT,PBS and Hydrocortisone(HCT),collecting blood In 1 d,7 d,14d,21 d and 28 d via mouse tail vein,then marking the T cells with anti-CD3,anti-CD4,anti-CD25 three-colored immune fluorescence

  15. 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

  16. 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.

  17. Detection of peripheral blood CD4+ CD25high CD127low regulatory T cells in patients with B-cell non-Hodgkin lymphoma and its clinical significance%B细胞非霍奇金淋巴瘤患者外周血CD4+CD25high CD127low调节性T细胞水平及其临床意义

    Institute of Scientific and Technical Information of China (English)

    白敏; 王列样; 赵志强; 苏文; 苏丽萍; 郑玉萍

    2014-01-01

    目的 探讨外周血CD4+ CD25high CD127low调节性T细胞(Treg细胞)在B细胞非霍奇金淋巴瘤(B-NHL)患者外周血中表达水平及其临床意义.方法 采用流式细胞术检测100例初诊B-NHL患者及50名健康对照者外周血CD4+ CD25high CD127low Treg细胞表达水平,进行统计学分析.结果 健康对照者外周血CD4+ CD25high CD127low Treg细胞中位表达水平为5.00%,初诊B-NHL患者为7.20%,两者之间差异具有统计学意义(P< 0.001).男性患者外周血CD4+ CD25high CD 127low Treg细胞水平高于女性患者(P<0.01),乳酸脱氢酶(LDH)增高患者外周血CD4+ CD25high CD127low Treg细胞水平高于LDH正常患者(P<0.01),Ⅲ~Ⅳ期患者外周血CD4+C D25high CD 127low Treg细胞水平较Ⅰ~Ⅱ期患者增高(P<0.01),有B症状患者外周血CD4+ CD25high CD127low Treg细胞水平高于无B症状患者(P<0.01).而不同年龄、国际预后指数评分、有无大包块患者之间外周血CD4+ CD25high CD 127low Treg细胞水平差异均无统计学意义(均P>0.05).结论 B-NHL患者体内存在免疫抑制,在男性、LDH增高、有B症状及晚期患者中CD4+ CD25high CD127low Treg细胞水平明显增高.检测其水平对于判断B-NHL的预后有一定价值.%Objective To detect peripheral blood level of CD4+ CD25high CD127low regulatory T (Treg) cells in patients with B cell non-Hodgkin lymphoma (B-NHL) and to explore its clinical significance.Methods The levels of peripheral blood CD4+ CD25high CD127low Treg cells of 100 newly diagnosed patients with B-NHL and 50 healthy adults were detected and analyzed by flow cytometry.Results The levels of peripheral blood CD4+ CD25high CD12low Treg cells were 5.00 % and 7.20 % in healthy adults and newly diagnosed B-NHL patients,respectively.The difference was statistically significant (P < 0.001).The level of peripheral blood CD4+ CD25high CD127low Treg cells was significantly higher in the male patients than that in the female (P < 0

  18. A Novel Alpha Cardiac Actin (ACTC1) Mutation Mapping to a Domain in Close Contact with Myosin Heavy Chain Leads to a Variety of Congenital Heart Defects, Arrhythmia and Possibly Midline Defects

    Science.gov (United States)

    Augière, Céline; Mégy, Simon; El Malti, Rajae; Boland, Anne; El Zein, Loubna; Verrier, Bernard; Mégarbané, André; Deleuze, Jean-François; Bouvagnet, Patrice

    2015-01-01

    Background A Lebanese Maronite family presented with 13 relatives affected by various congenital heart defects (mainly atrial septal defects), conduction tissue anomalies and midline defects. No mutations were found in GATA4 and NKX2-5. Methods and Results A set of 399 poly(AC) markers was used to perform a linkage analysis which peaked at a 2.98 lod score on the long arm of chromosome 15. The haplotype analysis delineated a 7.7 meganucleotides genomic interval which included the alpha-cardiac actin gene (ACTC1) among 36 other protein coding genes. A heterozygous missense mutation was found (c.251T>C, p.(Met84Thr)) in the ACTC1 gene which changed a methionine residue conserved up to yeast. This mutation was absent from 1000 genomes and exome variant server database but segregated perfectly in this family with the affection status. This mutation and 2 other ACTC1 mutations (p.(Glu101Lys) and p.(Met125Val)) which result also in congenital heart defects are located in a region in close apposition to a myosin heavy chain head region by contrast to 3 other alpha-cardiac actin mutations (p.(Ala297Ser),p.(Asp313His) and p.(Arg314His)) which result in diverse cardiomyopathies and are located in a totally different interaction surface. Conclusions Alpha-cardiac actin mutations lead to congenital heart defects, cardiomyopathies and eventually midline defects. The consequence of an ACTC1 mutation may in part be dependent on the interaction surface between actin and myosin. PMID:26061005

  19. 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.

  20. 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.

  1. 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.

  2. Is there any relationship between PSA and increased peripheral CD4+CD25highFOX3+ Treg in prostate cancer patients?

    Directory of Open Access Journals (Sweden)

    Yigit Akin

    2011-09-01

    Full Text Available Introduction: The aims of this study were fi rst, to determine whether peripheral levels of CD4+CD25highFoxp3+ regulatory T cells (Treg are elevated in Prostate Cancer (PCa patients, and second, to determine the directcorrelation between peripheral Treg and total serum Prostate Specifi c Antigen (PSA levels in these patients.Methods: Peripheral Blood Mononuclear Cells from 56 subjects undergoing diagnostic prostate biopsies (PSA ≥ 2.5 ng/ml were analyzed for Treg numbers. The association between the peripheral Treg and serum PSA values was fi rst determined in the entire population, including people with no prostate pathology and PCa and Benign Prostate Hyperplasia (BPH patients, and second, in nine PCa patients before and after curative prostatectomy.Results: This project was performed in Akdeniz University immunology laboratory and urology out patient clinic from 2008 to 2010. Peripheral Treg frequencies were signifi cantly increased in PCa patients (n = 19, 3.23 ± 1.59 compared with BPH patients (n = 27, 1.66 ± 0.80 and healthy subjects (n = 10, 1.08 ± 0.43 (p < 0.01. The percentage of Treg in BPH patients was also signifi cantly higher than that of healthy subjects (p < 0.01. Importantly, the increase in BPH and PCa patients paralleled the elevation in total serum PSA levels, demonstrating a strong positive correlation (r = 0.75; p < 0.01.Conclusion: These results demonstrate that peripheral Treg densities are correlated with PSA in BPH and PCa patients, suggesting that PSA may have a role in Treg induction and/or maintenance in Treg in these people.

  3. 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.

  4. PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+CD25Hi regulatory T cells

    Science.gov (United States)

    Lau, Roy; Yu, Daohai; Zhu, Weiwei; Korman, Alan; Weber, Jeffrey

    2009-01-01

    Regulatory CD4+CD25Hi T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. However, the underlying mechanisms by which they impact antigen-specific CD8+ immune responses in cancer patients and how they interact with each other under physiologic conditions remain unclear. Herein, we examined the relationship of PD-1 and its abrogation to the function of Treg in patients with melanoma using short-term in vitro assays to generate melanoma-specific T cells. We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients’ peripheral blood. Programmed death ligand (PD-L) 1 expression was also detected on patients’ Treg. PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-γ and IL-2 or INF-γ and tumor necrosis factor-α co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. PD-1 blockade also resulted in down-regulation of intracellular FoxP3 expression by Treg. These data suggest that PD-1 is importantly implicated in the regulation of Treg function in melanoma patients. PMID:19651643

  5. 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.

  6. 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

  7. Influence of Bone Marrow Mesenchymal Stem Cells on CD4 +CD25 +Treg Cells of Rat Heart Failure%骨髓间充质干细胞对鼠心力衰竭CD4+CD25+Treg 细胞的影响

    Institute of Scientific and Technical Information of China (English)

    陶恩学

    2014-01-01

    目的:研究骨髓间充质干细胞在鼠心力衰竭中对CD4+CD25+Treg细胞的影响。方法制作动物模型,雄性SD大鼠随机分为对照组A和模型组,模型组定期用阿霉素腹腔注射,对照组A用同等剂量生理盐水腹腔注射,每周1次,共6次,最后一次注射完成后继续喂养2周,行超声心动图检测左心室收缩末期容积( LVESV )、左室舒张末期容积( LVEDV )、左室射血分数( LVEF);并抽血通过流式细胞仪检测Tregs细胞。在最后一次注射完阿霉素1周后,分离、培养、扩增SD大鼠骨髓间充质干细胞(BMMSCs)。再将上述存活的模型组随机分为干预组,经尾静脉移植骨髓间充质干细胞组动物,对照组B,经尾静脉给予同等剂量生理盐水,分别于移植后第4周抽血通过流式细胞仪检测Tregs细胞,并行超声心动图检测LVESV,LVEDV,LVEF。结果①对照组A,B比较,LVESV,LVEF明显减低(P<0.05),而LVEDV明显升高(P<0.05)。②对照组A,B比较,CD4+CD25+Treg细胞的百分比明显减低( P<0.05)。结论骨髓间充质干细胞移植后可以上调CD4+CD25+Treg细胞,从而抑制扩张型心肌病中的免疫反应,改善心功能。%Objective To study the effect of bone marrow mesenchymal stem cells in the mouse heart failure on CD 4 +CD25 +Treg cells.Methods Male SD rats were randomly divided into control group A (n=10) and model group(n=20),and were treated regularly with intraperitoneal injection of doxorubicin in the model group and the same dose of normal saline in the control group weekly for a total of six times.Left ventricular end systolic volume (LVESV),left ventricular end diastolic volume (LVEDV),left ventricular ejection fraction ( LVEF) and blood Tregs cells were tested by Echocardiography and FlowCytometry respectively after two -week-feeding of the last injection . SD rat bone marrow mesenchymal stem cells (BMMSCs

  8. A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel.

    Science.gov (United States)

    Ji, Xiaonan; Shen, Yanli; Sun, Hao; Gao, Xiangdong

    2016-08-01

    Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.

  9. A case of subepidermal blistering disease with autoantibodies to multiple laminin subunits who developed later autoantibodies to alpha-5 chain of type IV collagen associated with membranous glomerulonephropathy.

    Science.gov (United States)

    Sueki, Hirohiko; Sato, Yoshinori; Ohtoshi, Shinpei; Nakada, Tokio; Yoshimura, Ashio; Tateishi, Chiharu; Borza, Dorin-Bogdan; Fader, William; Ghohestani, Reza F; Hirako, Yoshiaki; Koga, Hiroshi; Ishii, Norito; Tsuchisaka, Atsunari; Qian, Hua; Li, Xiaoguang; Hashimoto, Takashi

    2015-09-01

    We report a 68-year-old Japanese female patient with subepidermal blistering disease with autoantibodies to multiple laminins, who subsequently developed membranous glomerulonephropathy. At skin disease stage, immunofluorescence demonstrated IgG anti-basement membrane zone antibodies reactive with dermal side of NaCl-split skin. Immunoblotting of human dermal extract, purified laminin-332, hemidesmosome-rich fraction and laminin-521 trimer recombinant protein (RP) detected laminin γ-1 and α-3 and γ-2 subunits of laminin-332. Three years after skin lesions disappeared, nephrotic symptoms developed. Antibodies to α-3 chain of type IV collagen (COL4A3) were negative, thus excluding the diagnosis of Goodpasture syndrome. All anti-laminin antibodies disappeared. Additional IB and ELISA studies of RPs of various COL4 chains revealed reactivity with COL4A5, but not with COL4A6 or COL4A3. Although diagnosis of anti-laminin γ-1 (p200) pemphigoid or anti-laminin-332-type mucous membrane pemphigoid could not be made, this case was similar to previous cases with autoantibodies to COL4A5 and/or COL4A6.

  10. 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

  11. 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

  12. Integrability and soliton solutions for an inhomogeneous generalized fourth-order nonlinear Schrödinger equation describing the inhomogeneous alpha helical proteins and Heisenberg ferromagnetic spin chains

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Pan [State Key Laboratory of Information Photonics and Optical Communications, Beijing University of Posts and Telecommunications, Beijing 100876 (China); School of Science, Beijing University of Posts and Telecommunications, P.O. Box 122, Beijing 100876 (China); Tian, Bo, E-mail: tian.bupt@yahoo.com.cn [State Key Laboratory of Information Photonics and Optical Communications, Beijing University of Posts and Telecommunications, Beijing 100876 (China); School of Science, Beijing University of Posts and Telecommunications, P.O. Box 122, Beijing 100876 (China); Jiang, Yan; Wang, Yu-Feng [State Key Laboratory of Information Photonics and Optical Communications, Beijing University of Posts and Telecommunications, Beijing 100876 (China); School of Science, Beijing University of Posts and Telecommunications, P.O. Box 122, Beijing 100876 (China)

    2013-02-15

    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.

  13. Effect of acrolein exposure on the percentage of CD4 + CD25 + regulatory T cells and expression of transcription factor Foxp3 in asthmatic rats%丙烯醛暴露对哮喘大鼠CD4+CD25+调节性T细胞及转录因子Foxp3表达的影响

    Institute of Scientific and Technical Information of China (English)

    魏明; 涂玲; 梁颖红; 刘佳; 张俊华; 龚艳杰

    2012-01-01

    Objective This work was intended to investigate the effect of acrolein fog exposure on the ratio of CD4 + CD25 + regulatory T cells(Treg) and expression of transcription factor Foxp3 in asthmatic rats.Methods Sixty 6 - 8 weeks male Wistar rats were randomly divided into 4 groups according to random number table ( 15 rats for each group ) which were control group (animnals were treated with saline ),aerosolized ovalbumin( OVA )exposure group,acrolein exposure group and combined OVA and aerolein fog exposure group,respectively.The rats were exposed to air or/and to saline or OVA aerosol for 6 - 8 weeks respectively.24 h after the last challenge,4 ml of peripheral blood and lung tissue were collected from each rat.The percentage of CD4 + CD25 + T cells was determined by flow cytometry analysis.The concentration of interleukin-4(IL-4) and γ-interferon (IFN-γ)in peripheral blood and lung homogenates were measured by ELISA.The protein expression of Foxp3 in the lung was detected by Western blotting.Results The percentage of CD4 + CD25+ T cells in aerosolized OVA group( (6.23 ± 1.1 1 )% )was significantly lower than that in the normal saline group( ( 9.97 ± 1.23 )% ) ( P < 0.01 ).The percentage of CD4 + CD25 + T cells ((3.26 ±0.84)% )in OVA combined acrolein fog exposure group was remarkably lower than that in the aerosolized OVA exposure group and in the normal saline group( P < 0.01 ).11-4 in both plasma and lung ( (22.57 ±4.34),(0.86 ±0.12) ng/L) was significantly increased in the OVA exposed rats compared with the normal saline group( ( 11.57 ±2.86),(0.31 ±0.10) ng/L) ( P <0.01 ).Further remarkable increase in IL-4 of both plasma and lung tissue was observed in the group exposed to both OVA and acrolein ( ( 34.32 ± 6.21 ),( 1.45 ±0.32)ng/L) compared with the aerosolized OVA exposure group and the normal saline group( P < 0.05 ).γ-IFN of plasma and lung tissue in OVA exposed group ( ( 59.67 ± 20.12 ),( 0.56 ±0.17)ng/L) was significantly

  14. Relationship of CD4+ CD25hi Regulatory T(Treg)Cells to Disease Progression in HIV-infected Patients%HIV/AIDS患者疾病进程与CD4+CD25hi调节性T细胞之间相关性研究

    Institute of Scientific and Technical Information of China (English)

    宋淑静; 冯鑫; 郭晶晶; 刘亚楠; 伦文辉; 魏红山; 刘顺爱

    2009-01-01

    目的 通过分析不同阶段HIV感染者外周血CD4+CD25hi调节性T细胞(CD4+CD25hiregulatory T cells,Treg cells)与外周血免疫状态和病毒载量的相关性,探讨Treg细胞对HIV/AIDS发病进程的影响.方法 采集116例HIV感染者和21例正常人对照外周血,用4色流式细胞术进行CD4+和CD8+T细胞绝对数计数;用3色流式细胞术进行Treg细胞测定;用荧光定量PCR法进行HIVRNA载晕测定.实验数据用回归统计学方法和T检验方法进行分析.结果 HIV感染者外周血Treg细胞频率在HIV感染初期显著下降,之后随着疾病的进程逐渐升高.在CD4+T细胞大于300/μl的患者低于正常对照组,在CD4+T细胞小于100/μl的患者高于正常对照组,差异具有统计学意义.Treg细胞频率与CD4+T淋巴细胞绝对数和CD4+/CD8+之间均呈负相关.其相关系数r和P值各为r=-0.564,P<0.001和r=-0.377,P<0.001;Treg细胞频率与血浆HIV病毒载量呈正相关,其相关系数r=0.514.P<0.001.结论 CD4+CD25hi Treg细胞可能是参与艾滋病免疫发病机理的重要细胞,在HIV感染发病进程的不同阶段具有不同的意义,其确切机制有待进行进一步研究.%Objective Analyzing the relationships between peripheral blood CD4+ CD25hi regulatory T (Treg)cells and peripheral blood immune status or plasma HIV-1 viral load in HIV-infected individuMs,so as to determine whether Treg were related to the progression of HIV-infected disease.Methods116 HIV-infected patients in different stages and 21 healthy control individuals were included in this study.The CD4+ and CD8+ T cell counts were determined by a standard 4-color flow cytometry technique.The Treg cells were examined with 3-color immune staining flow cytometry.The plasma HIV-1 viral load was detected by real time PCR.Results The frequencies of Treg cells decreased in HIV-infected individuals with high CD4+ T cell counts(>300/μl)compared with normal controls.With the progression of disease the frequencies

  15. 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

  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.

    Directory of Open Access Journals (Sweden)

    Jannie Marie Sand

    Full Text Available OBJECTIVES: 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. METHODS: Fragments of type IV collagen cleaved in vitro by MMP-12 were identified by mass spectrometry, and two were chosen for ELISA development due to their unique sequences. The assays were evaluated using samples from a carbon tetrachloride (CCl₄ rat model of liver fibrosis and from patients with idiopathic pulmonary fibrosis (IPF or chronic obstructive pulmonary disease (COPD. RESULTS: Two technically robust ELISAs were produced using neo-epitope specific monoclonal antibodies. Mean serum C4M12a1 levels were significantly elevated in CCl₄-treated rats compared with controls in weeks 12, 16, and 20, with a maximum increase of 102% at week 16 (p < 0.0001. Further, C4M12a1 levels correlated with the total collagen content of the liver in CCl₄-treated rats (r = 0.43, p = 0.003. Mean serum C4M12a3 levels were significantly elevated in patients with mild, moderate, and severe IPF, and COPD relative to healthy controls, with a maximum increase of 321% in COPD (p < 0.0001. CONCLUSIONS: Two assays measuring C4M12a1 and C4M12a3 enabled quantification of MMP mediated degradation of type IV collagen in serum. C4M12a1 was elevated in a pre-clinical model of liver fibrosis, and C4M12a3 was elevated in IPF and COPD patients. This suggests the use of these assays to investigate pathological remodeling of the basement membrane in different organs. However, validations in

  17. Increase of Circulating CD4(+)CD25(high)Foxp3(+) 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)

    2010-01-01

    in patients with metastatic renal cell carcinoma on the frequency of CD4(+) CD25(high)Foxp3(+) 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 Treg cells decreased when patients...... had been off IL-2 treatment for only 8 days, but remained higher than pretreatment levels. A functional assay showed that isolated Treg cells were capable of inhibiting proliferation of responder cells. Also, in vitro studies showed that coculture of mature DCs, autologous T cells and IL-2 leads...... to an increase in the number of Treg cells whereas IL-21 does not stimulate the induction of Treg cells. These findings demonstrate that even low doses of IL-2 in combination with DC vaccination are able to expand CD4(+)CD25(+)Foxp3(+) Treg cells in vivo in metastatic renal cell carcinoma patients. Further...

  18. Clinical significance of detection of CD_4~+CD_(25)~(high)CD_(127)~(low) regulatory T cells in peripheral blood of NHL patients%非霍奇金淋巴瘤患者外周血CD_4~+CD_(25)~(high)CD_(127)~(low)调节性T细胞检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    赵志强; 张巧花; 苏文; 侯淑玲; 贺建霞

    2010-01-01

    目的 观察非霍奇金淋巴瘤(NHL)患者外周血CD_4~+CD_(25)~(high)CD_(127)~(low)调节性T细胞(Treg细胞)亚群水平的变化,初步探讨其临床意义.方法 采用流式细胞术检测65例NHL患者及29名健康人外周血中Treg细胞,并进行统计分析.结果 在65例NHL患者的外周血中Treg细胞的比例为(6.72±1.38)%,高于健康对照组(5.65±0.68)%(P0.05).结论 Treg细胞为免疫抑制细胞,可由肿瘤诱导产生,肿瘤患者外周血中Treg细胞高于健康对照组,且随着患者临床分期的增加,Treg细胞比值升高,Treg细胞比值可以作为临床评估瘤负荷的指标.%Objective To investigate the change of CD_4~+CD_(25)~(high)CD_(127)~(low)> regulatory T cells (Trcg cells) sub-group level in peripheral blood of non-Hodgkin lymphama (NHL) patients, and to explore its clinical significance. Methods Treg cells levels in peripheral blood of lymphoma patients and normal were detected by flow cytometry, followed by statistical analysis. Results In the 65 cases of NHL patients, Treg cells in peripheral blood were (6.72±1.38) %, higher than that in the normal control group (5.65±0.68) % (P 0.05, normal control group (5.65±0.68) %, patients with normal LDH group (6.97±1.20) %, patients with lactate dehydrogenase (6.54±1.02) %]. Conclusion Treg cells induced by tumor and could inhibit the immune cells, Treg cells percentage in peripheral blood of tumor patients is higher than that the normal control group, and increased with the clinical staging, so the percentage of Treg cells may serve as a clinical indicator to evaluate tumor load.

  19. 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.

  20. In vitro inhibition of enterobacteria-reactive CD4+CD25- T cells and suppression of immunoinflammatory colitis in mice by the novel immunomodulatory agent VGX-1027

    DEFF Research Database (Denmark)

    Mangano, Katia; Sardesai, Niranjan; D'Alcamo, Maria;

    2008-01-01

    of colitis in vivo. The beneficial effect in this model was associated with reduced colonic production of proinflammatory cytokines such as interleukin (IL)-1beta, TNF-alpha, IL-12p70 and interferon (IFN)-gamma and lower content of nuclear factor (NF)-kappaB (p65). These findings seem to warrant...

  1. Effect of 1,25-(OH) 2-VitD3 combined with spleen ammonia peptide oral freeze dry powder on CD4+CD25+T cells, TGF-β1 and VEGF in patients with asthma%1,25二羟维生素D3联合脾氨肽口服冻干粉对哮喘CD4+CD25+T细胞、TGF-β1及VEGF影响研究

    Institute of Scientific and Technical Information of China (English)

    高志刚; 袁永红; 詹建华; 潘开宇

    2016-01-01

    目的 探讨1,25-二羟维生素D3联合脾氨肽口服冻干粉对哮喘患者CD4+ CD25+T细胞、TGF-β1及VEGF的影响.方法 收集56例支气管哮喘患者,随机分为对照组和实验组,每组各28例,分别给予相应的药物治疗,治疗结束后,对所有患者的静脉血CD4+ CD25+T细胞水平、血清TGF-β1、VEGF水平、ACT评分及肺功能情况进行检测.结果 治疗后,与对照组比较,实验组患者静脉血CD4+CD25+T细胞水平较高(P<0.05);血清TGF-β1水平较高(P<0.05);血清VEGF水平较低(P <0.05);FEV1%、FEV1/FVC值较高(P<0.05);ACT评分较高(P<0.05).结论 1,25-二羟维生素D3联合脾氨肽口服冻干粉能够显著升高支气管哮喘患者静脉血CD4+ CD25+T细胞水平及血清TGF-β1,降低血清VEGF水平,提高免疫力,改善肺功能和治疗效果.

  2. CD4+CD25+调节性T细胞与Th17细胞在寻常型银屑病中的表达%Role of CD4+CD25+ regulatory T cells and Th17 cells in patients with psoriasis vulgaris

    Institute of Scientific and Technical Information of China (English)

    张玉丽; 王逸飞; 张春敏

    2016-01-01

    目的::检测外周血中CD4+CD25+调节性T细胞(简称Treg细胞)与Th17细胞在寻常型银屑病( PV)中的表达。方法:34例寻常型银屑病患者,18例正常人作为对照。采用流式细胞术检测外周血中Treg细胞、FOXP3+Treg细胞及Th17细胞的表达水平。结果: PV患者外周血中Treg细胞比例和FOXP3+Treg细胞比例分别为(3.68±1.22)%和(0.53±0.19)%,低于正常对照组的(6.63±1.00)%和(0.76±0.14)%(P0.05) . Conclusion:The decrease in the expression of Treg cells and the increased response of Th17 cells may be the important factors for the immuno-logical imbalance in PV.

  3. C57BL/6小鼠EAE模型的建立及Foxp3、CD4~+CD25~+调节性T细胞检测%Establishment of experimental allergic encephalomyelitis in C57BL/6 mice and testing of expressions of Foxp3 and quantifies of CD4~+ CD25~+ regulatory T cells

    Institute of Scientific and Technical Information of China (English)

    翁益云; 夏君慧; 鲍剑虹; 张国勇; 张旭

    2010-01-01

    目的 以髓鞘少突胶质细胞糖蛋白细胞外免疫球蛋白样结构域(MOG~(Igd))为抗原免疫C57BL/6小鼠,建立实验性自身免疫性脑脊髓炎(EAE)模型,并检测CD4~+CD25~+T细胞、Foxp3 mRNA等指标的表达.方法 采用分子克隆技术诱导表达MOG~(Igd)-TrxA融合蛋白,纯化后以此融合蛋白为抗原于侧腹壁皮下多点注射免疫C57BL/6小鼠作为实验组(MOG组);同时以硫氧还蛋白(TrxA)、豚鼠脊髓匀浆(GPSCH)、生理盐水免疫小鼠分别作为阴性、阳性及正常对照组.双盲法连续早晚观察30 d,通过评估动物的临床神经功能、组织病理(HE染色和Kluver-Barrera法髓鞘染色、免疫组化法)情况,评价模型的质量.流式细胞仪(FACS)检测小鼠脾脏中CD4~+CD25~+调节性T细胞;real-time PCR检测Foxp3 mRNA的相对表达水平,并分析两者相关性.结果 MOG组及GPSCH组小鼠均呈慢性非缓解型病程,两组在发病时间、达峰时间、临床神经功能评分等方面差异均无统计学意义(P>0.05).TrxA组及正常对照组无一动物发病.模型组(包括MOG组和GPSCH组)动物HE染色可见血管周围炎性细胞浸润,胶质结节形成,髓鞘染色可见斑片状髓鞘脱失,大脑、小脑、脑干和脊髓均有不同程度受累.免疫组化定性和半定量分析显示MOG组和GPSCH组病灶周围炎症浸润处AQP-4表达与TrxA组相比明显增高(P0.05).相关性分析显示,模型组小鼠CD4~+ CD25~+调节性T细胞与Foxp3 mRNA表达水平间存在相关性(r=0.849,P0.05). However, neither in TrxA treated group nor in normal control group did animals exhibit clinical signs of EAE. Histologic sections of the brain and spinal cord taken from affected animals shew perivascular infiltration of mononuclear cells, gliosis, and multifocal demyelination. Lesions scattered throughout the CNS including brainstem, spinal cord, cerebellum, and penventricular white matter. There were significant differences between MOG group and TrxA group

  4. 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

  5. Bilinear forms and soliton solutions for a fourth-order variable-coefficient nonlinear Schrödinger equation in an inhomogeneous Heisenberg ferromagnetic spin chain or an alpha helical protein

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jin-Wei; Gao, Yi-Tian, E-mail: gaoyt163@163.com; Wang, Qi-Min; Su, Chuan-Qi; Feng, Yu-Jie; Yu, Xin

    2016-01-15

    In this paper, a fourth-order variable-coefficient nonlinear Schrödinger equation is studied, which might describe a one-dimensional continuum anisotropic Heisenberg ferromagnetic spin chain with the octuple–dipole interaction or an alpha helical protein with higher-order excitations and interactions under continuum approximation. With the aid of auxiliary function, we derive the bilinear forms and corresponding constraints on the variable coefficients. Via the symbolic computation, we obtain the Lax pair, infinitely many conservation laws, one-, two- and three-soliton solutions. We discuss the influence of the variable coefficients on the solitons. With different choices of the variable coefficients, we obtain the parabolic, cubic, and periodic solitons, respectively. We analyse the head-on and overtaking interactions between/among the two and three solitons. Interactions between a bound state and a single soliton are displayed with different choices of variable coefficients. We also derive the quasi-periodic formulae for the three cases of the bound states.

  6. 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.

  7. 巨细胞病毒感染致婴幼儿喘息患儿中瘦素、CD4CD25Treg和TLR4的表达

    Institute of Scientific and Technical Information of China (English)

    朱春晖; 陈强; 朱庆雄; 柯江维

    2012-01-01

    Objective The influence of cytomegalovirus infection on the leptin, CD4+CD25+ regulatory T cell and Toll-like receptor.Methods Using PCR to detect the phlegm and serum CMV DNA level of 69 wheezing infants and 28 healthy volunteers and compare the positive rates.detect the leptin level of cytomegalovirus infectious infants with radioimmunoassay in 24 hours after admission, 24 hours after ganciclovir treatment and 12 weeks after the treatment,the CD4+CD25+Treg percentage of CD4+T in peripheral blood and TLR4 expression in monocytes cell surface with flow cytometry.follow-up the wheezing in out - patient clinic or through phone call.Results (1)37 of wheezing infants suffered cytomegalovirus infection,the positive rates was 53.62%,was much higher than that in healthy volunteers group(1/28,3.57%)(p0.05).24h after the treatment:the leptin and TLR4 level in the group accepted ganciclovir treatment, the group refused ganciclovir treatment and group non- cytomegalovirus infection was lower than that before treatment,the level among the three groups has no significant difference(p>0.05); the CD4+CD25+Treg percentage increased after treatment(p0.05).治疗结束24h内:更昔洛韦治疗组、非更昔洛韦治疗组和非巨细胞病毒感染组瘦素水平均较治疗前下降,组间无明显差异(p>0.05),更昔洛韦治疗后CD4+CD25+Treg百分比增高,差异有统计学意义(p<0.05),TLR4水平较治疗前明显下降(p<0.01),且低于同期非更昔洛韦治疗组TLR4水平(p<0.05).治疗后12周:更昔洛韦治疗组瘦素及TLR4水平低于非更昔洛韦治疗组和非巨细胞病毒感染组,CD4+CD25+Treg百分比高于非更昔洛韦治疗组和非巨细胞病毒感染组,差异有统计学意义(p<0.05);非巨细胞病毒感染组瘦素水平、CD4+CD25+Treg百分比及TLR4水平与入院后24小时内及治疗结束24小时内比较无明显差异.(4)更昔洛韦治疗后随访2年患儿喘息次数明显减少(p<0.05).结论(1)巨细胞病毒感染与婴

  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. 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.

  10. 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

  11. Increase in TGF-β secreting CD4⁺CD25⁺ FOXP3⁺ T regulatory cells in anergic lepromatous leprosy patients.

    Directory of Open Access Journals (Sweden)

    Chaman Saini

    Full Text Available BACKGROUND: Lepromatous leprosy caused by Mycobacterium leprae is associated with antigen specific T cell unresponsiveness/anergy whose underlying mechanisms are not fully defined. We investigated the role of CD25(+FOXP3(+ regulatory T cells in both skin lesions and M.leprae stimulated PBMC cultures of 28 each of freshly diagnosed patients with borderline tuberculoid (BT and lepromatous leprosy (LL as well as 7 healthy household contacts of leprosy patients and 4 normal skin samples. METHODOLOGY/PRINCIPLE FINDINGS: Quantitative reverse transcribed PCR (qPCR, immuno-histochemistry/flowcytometry and ELISA were used respectively for gene expression, phenotype characterization and cytokine levels in PBMC culture supernatants. Both skin lesions as well as in vitro antigen stimulated PBMC showed increased percentage/mean fluorescence intensity of cells and higher gene expression for FOXP3(+, TGF-β in lepromatous (p<0.01 as compared to tuberculoid leprosy patients. CD4(+CD25(+FOXP3(+ T cells (Tregs were increased in unstimulated basal cultures (p<0.0003 and showed further increase in in vitro antigen but not mitogen (phytohemaglutinin stimulated PBMC (iTreg in lepromatous as compared to tuberculoid leprosy patients (p<0.002. iTregs of lepromatous patients showed intracellular TGF-β which was further confirmed by increase in TGF-β in culture supernatants (p<0.003. Furthermore, TGF-β in iTreg cells was associated with phosphorylation of STAT5A. TGF-β was seen in CD25(+ cells of the CD4(+ but not that of CD8(+ T cell lineage in leprosy patients. iTregs did not show intracellular IFN-γ or IL-17 in lepromatous leprosy patients. CONCLUSIONS/SIGNIFICANCE: Our results indicate that FOXP3(+ iTregs with TGF-β may down regulate T cell responses leading to the antigen specific anergy associated with lepromatous leprosy.

  12. CD4+CD25+FoxP3+ Regulatory Tregs inhibit fibrocyte recruitment and fibrosis via suppression of FGF-9 production in the TGF-b1 exposed murine lung

    Directory of Open Access Journals (Sweden)

    Xueyan ePeng

    2014-05-01

    Full Text Available Pulmonary fibrosis is a difficult to treat, often fatal disease whose pathogenesis involves dysregulated TGF-b1 signaling. CD4+CD25+FoxP3+ Regulatory T cells (Tregs exert important effects on host tolerance and arise from naïve CD4+ lymphocytes in response to TGF-b1. However the precise contribution of Tregs to experimentally induced murine lung fibrosis remains unclear. We sought to better understand the role of Tregs in this context. Using a model of fibrosis caused by lung specific inducible overexpression of the bioactive form of the human TGF-b1 gene we find that Tregs accumulate in the lung parenchyma within five days of transgene activation and that this enhancement persists to at least fourteen days. Anti-CD25 Antibody mediated depletion of Tregs causes increased detection of soluble collagen and of intrapulmonary CD45+CD34+Col Ia1 fibrocytes. These findings are accompanied by enhanced local concentrations of the classical inflammatory mediators CD40L, TNF-a, and IL-1a, along with the neuroimmune molecule fibroblast growth factor 9 (FGF-9, also known as glial activating factor. FGF-9 expression localizes to structural cells and alveolar macrophages in this model and antibody mediated neutralization of FGF-9 results in attenuated detection of intrapulmonary collagen and fibrocytes without affecting Treg quantities. These data indicate that CD4+CD25+FoxP3+ Tregs attenuate TGF-b1 induced lung fibrosis and fibrocyte accumulation in part via suppression of FGF-9.

  13. CD4+CD25+FoxP3+ Regulatory Tregs inhibit fibrocyte recruitment and fibrosis via suppression of FGF-9 production in the TGF-β1 exposed murine lung.

    Science.gov (United States)

    Peng, Xueyan; Moore, Meagan W; Peng, Hong; Sun, Huanxing; Gan, Ye; Homer, Robert J; Herzog, Erica L

    2014-01-01

    Pulmonary fibrosis is a difficult to treat, often fatal disease whose pathogenesis involves dysregulated TGF-β1 signaling. CD4+CD25+FoxP3+ Regulatory T cells ("Tregs") exert important effects on host tolerance and arise from naïve CD4+ lymphocytes in response to TGF-β1. However, the precise contribution of Tregs to experimentally induced murine lung fibrosis remains unclear. We sought to better understand the role of Tregs in this context. Using a model of fibrosis caused by lung specific, doxycycline inducible overexpression of the bioactive form of the human TGF-β1 gene we find that Tregs accumulate in the lung parenchyma within 5 days of transgene activation and that this enhancement persists to at least 14 days. Anti-CD25 Antibody mediated depletion of Tregs causes increased accumulation of soluble collagen and of intrapulmonary CD45+Col Iα1 fibrocytes. These effects are accompanied by enhanced local concentrations of the classical inflammatory mediators CD40L, TNF-α, and IL-1α, along with the neuroimmune molecule fibroblast growth factor 9 (FGF-9, also known as "glial activating factor"). FGF-9 expression localizes to parenchymal cells and alveolar macrophages in this model and antibody mediated neutralization of FGF-9 results in attenuated detection of intrapulmonary collagen and fibrocytes without affecting Treg quantities. These data indicate that CD4+CD25+FoxP3+ Tregs attenuate TGF-β1 induced lung fibrosis and fibrocyte accumulation in part via suppression of FGF-9.

  14. Pathophysiological significance of the two-pore domain K+ channel K2P5.1 in splenic CD4+CD25− T cell subset from a chemically-induced murine inflammatory bowel disease model

    Science.gov (United States)

    Nakakura, Sawa; Matsui, Miki; Sato, Aya; Ishii, Mizuki; Endo, Kyoko; Muragishi, Sayaka; Murase, Miki; Kito, Hiroaki; Niguma, Hiroki; Kurokawa, Natsumi; Fujii, Masanori; Araki, Masatake; Araki, Kimi; Ohya, Susumu

    2015-01-01

    The alkaline pH-activated, two-pore domain K+ channel K2P5.1 (also known as TASK2/KCNK5) plays an important role in maintaining the resting membrane potential, and contributes to the control of Ca2+ signaling in several types of cells. Recent studies highlighted the potential role of the K2P5.1 K+ channel in the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The aim of the present study was to elucidate the pathological significance of the K2P5.1 K+ channel in inflammatory bowel disease (IBD). The degrees of colitis, colonic epithelial damage, and colonic inflammation were quantified in the dextran sulfate sodium-induced mouse IBD model by macroscopic and histological scoring systems. The expression and functional activity of K2P5.1 in splenic CD4+ T cells were measured using real-time PCR, Western blot, and fluorescence imaging assays. A significant increase was observed in the expression of K2P5.1 in the splenic CD4+ T cells of the IBD model. Concomitant with this increase, the hyperpolarization response induced by extracellular alkaline pH was significantly larger in the IBD model with the corresponding intracellular Ca2+ rises. The expression of K2P5.1 was higher in CD4+CD25− T cells than in CD4+CD25+ regulatory T cells. The knockout of K2P5.1 in mice significantly suppressed the disease responses implicated in the IBD model. Alternations in intracellular Ca2+ signaling following the dysregulated expression of K2P5.1 were associated with the disease pathogenesis of IBD. The results of the present study suggest that the K2P5.1 K+ channel in CD4+CD25− T cell subset is a potential therapeutic target and biomarker for IBD. PMID:26578971

  15. 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 ...... 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...

  16. Linfócitos T CD4+CD25+ e a regulação do sistema imunológico: perspectivas para o entendimento fisiopatológico da sepse

    OpenAIRE

    Rodrigo Siqueira-Batista; Andréia Patrícia Gomes; Sarah Fumian Milward de Azevedo; Rodrigo Roger Vitorino; Eduardo Gomes de Mendonça; Flávio Oliveira de Sousa; Alcione de Paiva Oliveira; Fábio Ribeiro Cerqueira; Sérgio Oliveira de Paula; Maria Goreti de Almeida Oliveira

    2012-01-01

    A resposta inflamatória sistêmica representa o evento patogênico central da sepse, subjazendo às manifestações clínicas e aos achados laboratoriais presentes nos enfermos. Inúmeras pesquisas têm demonstrado que os linfócitos T CD4+CD25+ - também conhecidos como células T reguladoras (Treg) - participam dos processos de desenvolvimento da sepse, em virtude de sua capacidade de suprimir a resposta imune. Com base nessas ideias, propôs-se, no presente artigo, a discussão do papel dos linfócitos ...

  17. 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 ...

  18. 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.

  19. Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma

    DEFF Research Database (Denmark)

    Hermann, G G; Geertsen, P F; von der Maase, H;

    1991-01-01

    schedule with continuous intravenous IL-2 infusion (3 x 10(6) units m-2 day-1) administered from days 1 to 5 and days 12 to 16. The white blood cell count and the absolute and relative number of neutrophils, lymphocytes, eosinophils and monocytes were recorded six times in peripheral blood during...... the treatment. Also the blood counts of T cell and NK cell subsets and cells expressing the T cell activation markers IL-2R alpha and VLA-1 were measured. The lymphokine-activated killer (LAK) cell cytotoxicity was measured either with or without additional in vitro stimulation by IL-2. Multivariate statistical...... analysis showed that the clinical responses were related to the administered dose of IL-2, to a low number of blood cells expressing IL-2 receptors and to a reduction in the blood monocyte count (P less than 0.05)....

  20. 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

  1. 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.

  2. 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.

  3. Analysis of mRNA expression for genes associated with regulatory T lymphocytes (CD25, FoxP3, CTLA4, and IDO) after experimental infection with bovine viral diarrhea virus of low or high virulence in beef calves.

    Science.gov (United States)

    Palomares, Roberto A; Hurley, David J; Woolums, Amelia R; Parrish, Jacqueline E; Brock, Kenny V

    2014-12-01

    Immunosuppression caused by bovine viral diarrhea virus (BVDV) has been associated with lymphocyte depletion, leukopenia and impairment of leukocyte function; however, no work has been done on the relationship between BVDV and regulatory T lymphocytes (Tregs). The objective of this study was to compare the mRNA expression of genes associated with Tregs (CD25, FoxP3, CTLA4, and IDO), after experimental infection of beef calves with low (LV) or high (HV) virulence BVDV. Thirty BVDV-naïve calves were randomly assigned to three groups. Calves were intra-nasally inoculated with LV (n=10, strain SD-1) or HV (n=10, strain 1373) BVDV or BVDV-free cell culture medium (control, n=10). Quantitative RT-PCR was used to determine the expression of target genes in tracheo-bronchial lymph nodes and spleen on day 5 post-infection. The mRNA expression of CD25 was up-regulated in tracheo-bronchial lymph nodes of LV (Pviral strains, or differences in viral infectivity of the host cells.

  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. Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model.

    Science.gov (United States)

    Zenclussen, Ana Claudia; Gerlof, Katrin; Zenclussen, Maria Laura; Sollwedel, André; Bertoja, Annarosa Zambon; Ritter, Thomas; Kotsch, Katja; Leber, Joachim; Volk, Hans-Dieter

    2005-03-01

    Mammalian pregnancy is thought to be a state of immunological tolerance. The mechanisms underlying this phenomenon are still poorly understood. Here, we determined whether an inappropriate function of T regulatory (Treg) cells is involved in the pathogenesis of spontaneous abortion. We evaluated spleen and decidual lymphocytes from CBA/J mice undergoing immunological abortion (DBA/2J-mated) or having normal pregnancy (BALB/c-mated) on day 14 of gestation for ex vivo cytokine production after PMA or paternal antigen (alloantigen) stimulation. Treg activity was characterized by quantifying CD4(+)CD25(+) cells, foxp3 expression, and interleukin-10 secretion. Decidual lymphocytes from abortion CBA/J mice contained a significantly higher frequency of interferon-gamma-producing T cells specific for paternal antigens compared to those from normal pregnancy (7.8% versus 2.7%, P abortion mice. Very interestingly, CD4(+)CD25(+) Treg cells from normal pregnant and nonpregnant CBA/J mice could inhibit both proliferation and interferon-gamma secretion of lymphocytes from abortion mice in vitro whereas in vivo prevention of fetal rejection could only be achieved after adoptive transfer of Treg cells from normal pregnant mice. Our data suggest that pregnancy-induced Treg cells play a vital role in maternal tolerance to the allogeneic fetus.

  6. 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.

  7. Correlation of the expression of CD4+CD25+CD127low/- regulatory T cells and transforming growth factor-β with primary rheumatoid arthritis%调节性T细胞和转化生长因子β与初发类风湿性关节炎相关性研究

    Institute of Scientific and Technical Information of China (English)

    罗莉; 罗德梅; 刘盼盼; 董旭南

    2011-01-01

    Objective To investigate the expressions of CD4+ CD25+ CD127low/- regulatory T cells and transforming growth factor-β in the peripheral blood of patients with primary and active rheumatoid arthritis and to explore its mechanism in the pathogenesis of rheumatoid arthritis. Methods The rates of CD4+ CD25+ CD127low/- regulatory T cells in the peripheral blood of 40 primary and active rheumatoid arthritis patients and 35 normal controls were evaluated with flow cytometry. The level of transforming growth factor-β in blood serum was detected with ELISA. All the data were analyzed.Results The positive rate of CD4+ CD25+ T cells in rheumatoid arthritis was significantly lower than that in normal controls(P<0.05). The positive rate of CD4+ CD25+ CD127low/- T cells in rheumatoid arthritis was lower than that in normal controls, but there was no significant difference(P>0.05).There were significant differences between the percentage of CD4+ CD25+ T cells and the percentage of CD4+CD25+CD127low/- T cells in two groups(P<0.05). The level of CD4+ CD25+ T cells was correlated with the level of CD4+ CD25+ CD127low/- T cells in both groups(P<0.05). The level of transforming growth factor-β in rheumatoid arthritis was higher than that in control group(P<0.01).Transforming growth factor-β was not correlated with the level of CD4+ CD25+ CD127low/- regulatory T cells or CD4+ CD25+ T cells in two groups (P> 0.05). The levels of CD4+ CD25+ CD127low/-regulatory T cells, CD4+ CD25+ T cells and transforming growth factor-β were not correlated with erythrocyte sedimentation rate, C-reactive protein, anticyclic citrullinated peptide antibody,antikeratin antibody, or rheumatoid factor level(P>0.05). Conclusion The decrease of CD4+ CD25+CD127low/- regulatory T cells may be correlated with cellular immunity disorder in rheumatoid arthritis. The mechanism of transforming growth factor-β is complex in rheumatoid arthritis.%目的:探讨CD4+CD25+CD127low/-调节性T细

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. $\\alpha_s$ 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.

  13. A glucocorticoid amplifies IL-2-induced selective expansion of CD4+CD25+FOXP3+ regulatory T cells in vivo and suppresses graft-versus-host disease after allogeneic lymphocyte transplantation

    Institute of Scientific and Technical Information of China (English)

    Yanhui Xie; Min Wu; Runhua Song; Jiexian Ma; Yi Shi; Wenming Qin; Youxin Jin

    2009-01-01

    Regulatory T (Treg) cells are a subpopulation of T cells that not only prevent autoimmunity, but also control a wide range of T cell-dependent immune responses. Glucocorticoid treatment (dexamethasone, or Dex) has been reported to amplify IL-2-mediated selective in vivo expansion of Treg cells. We simultaneously adminis-tered Dex and IL-2 to the donor in a murine allogeneic lymphocyte transplantation model to expand functional suppressive CD4+CD25+FOXP3+ T cells in the graft and to raise the regulatory T cell/effector T cell (Treg/ Teff) ratio to prevent graft-versus-host disease (GVHD). After combined treatment of the donor with Dex (5 mg/kg/day) and IL-2 (300,000 IU/mouse/day) for 3 days, grafts were subjected to flow cytometric analy-sis, and transplantation was carried out from male C57BL/6 mice to female BALB/c mice aged 8-12 weeks. Results showed that short-term simultaneous administration of Dex and IL-2 markedly expanded functional suppressive CD4+CD25+FOXP3+ T cells in the murine spleen. In this murine allogeneic transplan-tation model, the grafts from donors with Dex and IL-2 pre-treatment led to a longer survival time for the reci-pients than for the control group (median survival time> 60 day vs. 12 day, P = 0.0002). The ratio of Treg/Teff also increased remarkably (0.43 ±0.15 vs. 0.14± 0.01, P=0.01). This study demonstrated that co-stimulation with Dex and IL-2 selectively expanded functional CD4+CD25+FOXP3+ T cells in vivo, and that grafts from donors pre-treated with Dex and IL-2 led to longer survival time and greater suppression of GVHD after allogeneic transplantation. Thus, GVHD can be suppressed by the specific expansion of regulatory T cells with Dex and IL-2 in graft donors.

  14. 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.

  15. 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.

  16. Contribution of alpha3(IV)alpha4(IV)alpha5(IV) Collagen IV to the Mechanical Properties of the Glomerular Basement Membrane

    Science.gov (United States)

    Gyoneva, Lazarina

    The glomerular basement membrane (GBM) is a vital part of the blood-urine filtration barrier in the kidneys. In healthy GBMs, the main tension-resisting component is alpha3(IV)alpha4(IV)alpha5(IV) type IV collagen, but in some diseases it is replaced by other collagen IV isoforms. As a result, the GBM becomes leaky and disorganized, ultimately resulting in kidney failure. Our goal is to understanding the biomechanical aspects of the alpha3(IV)alpha4(IV)alpha5(IV) chains and how their absence could be responsible for (1) the initial injury to the GBM and (2) progression to kidney failure. A combination of experiments and computational models were designed for that purpose. A model basement membrane was used to compare experimentally the distensibility of tissues with the alpha3(IV)alpha4(IV)alpha5(IV) chains present and missing. The experiments showed basement membranes containing alpha3(IV)alpha4(IV)alpha5(IV) chains were less distensible. It has been postulated that the higher level of lateral cross-linking (supercoiling) in the alpha3(IV)alpha4(IV)alpha5(IV) networks contributes additional strength/stability to basement membranes. In a computational model of supercoiled networks, we found that supercoiling greatly increased the stiffness of collagen IV networks but only minimally decreased the permeability, which is well suited for the needs of the GBM. It is also known that the alpha3(IV)alpha4(IV)alpha5(IV) networks are more protected from enzymatic degradation, and we explored their significance in GBM remodeling. Our simulations showed that the more protected network was needed to prevent the system from entering a dangerous feedback cycle due to autoregulation mechanisms in the kidneys. Overall, the work adds to the evidence of biomechanical differences between the alpha3(IV)alpha4(IV)alpha5(IV) networks and other collagen IV networks, points to supercoiling as the main source of biomechanical differences, discusses the suitability of alpha3(IV)alpha4(IV)alpha

  17. Regulation by retinoids of luteinizing hormone/chorionic gonadotropin receptor, cholesterol side-chain cleavage cytochrome P-450, 3 beta-hydroxysteroid dehydrogenase/delta (5-4)-isomerase and 17 alpha-hydroxylase/C17-20 lyase cytochrome P-450 messenger ribonucleic acid levels in the K9 mouse Leydig cell line.

    Science.gov (United States)

    Lefèvre, A; Rogier, E; Astraudo, C; Duquenne, C; Finaz, C

    1994-12-01

    Vitamin A is a potent regulator of testicular function. We have reported that retinol (R) and retinoic acid (RA) induced a down regulation of luteinizing hormone/human chorionic gonadotropin (LH/CG) binding sites in K9 Leydig cells. In the present study we evaluated the effect of R and RA on LH/CG receptors, cholesterol side-chain cleavage cytochrome P-450 (P-450 scc), 17 alpha-hydroxylase/C17-20 lyase (P-450 17 alpha) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) mRNA levels in K9 mouse Leydig cells. To validate K9 cells as a model for studying Leydig cell steroidogenesis at the molecular level, we first investigated the effect of hCG on mRNA levels of the steroidogenic enzymes. P-450 scc, 3 beta HSD and P-450 17 alpha were expressed constitutively. The addition of 10 ng/ml hCG enhanced mRNA levels for the three genes within 2 h. Maximal accumulation of P-450 scc, P-450 17 alpha and 3 beta HSD mRNA in treated cells represents a 2.5-, 8.5- and 4-fold increase over control values, respectively. P-450 17 alpha expression reached a maximum by 4 h and then declined rapidly to return to control value by 24 h. The pattern of LH/CG receptor mRNAs in K9 cells was very similar to that of MA10 Leydig cells and showed six transcripts of 1.1, 1.6, 1.9, 2.6, 4.2 and 7.0 kb. Treatment of cells with R or RA resulted in a time- and dose-dependent decrease in all six species.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. 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.

  19. Sequences related to HLA-DRα chain on human chromosome 6: Restriction enzyme polymorphism detected with DCα chain probes.

    NARCIS (Netherlands)

    J. Trowsdale (John); J.S. Lee (Janet); J.E. Carey (Janet); F.G. Grosveld (Frank); J.G. Bodmer (Julia); W.F. Bodmer (Walter)

    1983-01-01

    markdownabstractThree sets of cosmid clones--containing the HLA-DR alpha chain gene and two additional related genes--were isolated from human genomic DNA libraries by using a cDNA probe for the HLA-DR alpha chain. Southern blot analysis using DNA from somatic cell hybrids indicated that all of the

  20. 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.

  1. 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...

  2. Evaluating Reverse Supply Chain Efficiency: Manufacturer's Perspective

    DEFF Research Database (Denmark)

    Kumar, M.; Tiwari, M. K.; Wong, K. Y.

    2014-01-01

    The paper aims to illustrate the use of fuzzy data envelopment analysis (DEA) in analyzing reverse supply chain (RSC) performance from the manufacturer's perspective. By using an alternative alpha-cut approach, the fuzzy DEA model was converted into a crisp linear programming problem, thereby...... usually ensures an environmentally friendly supply chain network, companies which have implemented RSC techniques since a longer duration do not necessarily have a more efficient supply chain in general....

  3. 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.

  4. 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.

  5. 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.

  6. Linfócitos T CD4+CD25+ e a regulação do sistema imunológico: perspectivas para o entendimento fisiopatológico da sepse

    Directory of Open Access Journals (Sweden)

    Rodrigo Siqueira-Batista

    2012-09-01

    Full Text Available A resposta inflamatória sistêmica representa o evento patogênico central da sepse, subjazendo às manifestações clínicas e aos achados laboratoriais presentes nos enfermos. Inúmeras pesquisas têm demonstrado que os linfócitos T CD4+CD25+ - também conhecidos como células T reguladoras (Treg - participam dos processos de desenvolvimento da sepse, em virtude de sua capacidade de suprimir a resposta imune. Com base nessas ideias, propôs-se, no presente artigo, a discussão do papel dos linfócitos Treg na sepse, com base na revisão da literatura com estratégia de busca definida (LILACS, PubMed e SciELO, tendo em vista duas abordagens principais: a participação dessas células nos processos de inflamação e imunidade, e as perspectivas de investigação fisiopatológica computacional da condição mórbida.

  7. The ACE inhibitors enalapril and captopril modulate cytokine responses in Balb/c and C57Bl/6 normal mice and increase CD4(+)CD103(+)CD25(negative) splenic T cell numbers.

    Science.gov (United States)

    Albuquerque, Deijanira; Nihei, Jorge; Cardillo, Fabíola; Singh, Ram

    2010-01-01

    Increasing evidence implies beneficial effects of angiotensin-converting enzyme (ACE) inhibitors beyond those of their original indications to control hypertension. One of the most attractive non-hemodynamic properties of ACE inhibitors is their ability to regulate cytokine production. The mechanism(s) underlying the role of ACE inhibitors on cytokine synthesis are not well understood but they have traditionally been attributed to the inhibition of angiotensin (Ang) II formation. In fact, it has been extensively demonstrated that ACE inhibitors decrease Ang II-induced production of proinflammatory cytokines and chemokines. However, it is not well described if inhibition of endogenous Ang II generation by ACE inhibitors modulates systemic cytokine production in mice. To verify that, in this work, we investigated the effects of treatment with the ACE inhibitors enalapril and captopril on cytokine synthesis in C57Bl/6 and Balb/c mice. Our results show that enalapril up regulates IL-10 produced by splenocytes from Balb/c and C57Bl/6 mice and captopril increased it only in Balb/c mice. Furthermore, CD4(+)CD103(+) presented increased IL-10 production after enalapril treatment. Enalapril as well as captopril short-term treatment enhanced IL-2 synthesis in Balb/c mice. Besides, enhanced IL-2 and IL-10 levels correlates with increased CD4(+)CD103(+)CD25(negative) T cells numbers in spleens from enalapril-treated mice.

  8. Adalimumab specifically induces CD3+ CD4+ CD25high Foxp3+ CD127− T-regulatory cells and decreases vascular endothelial growth factor plasma levels in refractory immuno-mediated uveitis: a non-randomized pilot intervention study

    Science.gov (United States)

    Calleja, S; Cordero-Coma, M; Rodriguez, E; Llorente, M; Franco, M; Ruiz de Morales, J G

    2012-01-01

    Aim To explore immunoregulatory and anti-inflammatory pathways specifically targeted by a subcutaneous anti-TNFαdrug—adalimumab—which might be relevant for controlling refractory uveitis. Design Non-randomized pilot intervention study on the effects of adalimumab on Treg populations and plasma VEGF levels in refractory uveitis patients. Inflammatory and immunological parameters were measured in 12 patients before therapy, and 1 and 6 months after therapy, and analyzed in the context of ophthalmological outcomes. The results were compared with those obtained in 10 systemic prednisone-treated uveitis patients. Results After 1 month of treatment, all patients responded, with 67% of adalimumab group and 80% of the corticosteroid group achieving inactivity (P=0.5). Unlike steroid-treated patients, a significant increase in T-regulatory CD4+ CD25high Foxp3+ CD127− cells was observed in adalimumab patients after 1 month of treatment, and maintained after 6 months (P=0.003). A significant adalimumab-specific drop in plasma VEGF was observed after 1 and 6 months of treatment (P=0.019). In every single patient, Tregs but not VEGF correlated with disease activity. Conclusions In refractory uveitis patients treated with adalimumab, clinical efficacy may be mediated through upregulation of Tregs in addition to modulation of VEGF-mediated inflammatory pathways. These biological properties, which were not observed in patients treated with corticosteroids, may reflect the specificity of TNF-αtargeting. PMID:22222264

  9. Monoclonal antibody based immunoassays to screen for alpha-thalassemia in adults

    Energy Technology Data Exchange (ETDEWEB)

    Epstein, N.; Than, K.A. Culp, K.M. [Isolab, Inc., Akron, OH (United States)] [and others

    1994-09-01

    Alpha-thalassemia (alpha-thal) is characterized by the absence or reduction in synthesis of the alpha-globin chain due to either deletions or other abnormalities involving the alpha-globin genes located on the short arm of chromosome 16. The diploid cells have four alpha chain genes. The deletion of one, two, three or all four of these genes could result in mild to a complete alpha chain deficiency known as the Hydrops fetalis syndrome or alpha-thal-1, which causes fetal death. It is important to develop a sensitive test to detect carriers of alpha-thal-1 trait for genetic counseling. It has recently been observed that the presence of minute amounts of zeta-globin chains (0.01-1%) could serve as a biological marker of alpha-thal carriers. Because high sensitivity is required, we constructed a monoclonal antibody-based immunoassay which can be analyzed either by colorimetric or fluorimetric methods. By testing blood samples from individuals of Southeast Asian ancestry, we were able to show that various forms and combinations of deletions or inactivations of two or three alpha-globin genes results in alpha-thalassemia conditions that have elevated levels of the zeta-chain. Sensitivity achieved in these tests was < 0.1% zeta chain, or as low as 5 ng zeta-chain. Data correlate with results from reversed phase HPLC.

  10. Complete amino acid sequence of the human alpha 5 (IV) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient

    DEFF Research Database (Denmark)

    Zhou, J; Hertz, Jens Michael; Leinonen, A;

    1992-01-01

    alleles. The mutation which was located to exon 23 was sequenced from a polymerase chain reaction-amplified product, and shown to be a G----T change in the coding strand. The mutation changed the GGT codon of glycine 521 to cysteine. The same mutation was found in one allele of the female cousin...

  11. Determination of {alpha}-nucleus potentials by {alpha}-elastic scattering and its implications for the {gamma}-process

    Energy Technology Data Exchange (ETDEWEB)

    Galaviz, D. E-mail: redondo@ikp.tu-darmstadt.de; Babilon, M.; Fueloep, Zs.; Gyuerky, Gy.; Mate, Z.; Hillier, R.; Mohr, P.; Rauscher, T.; Somorjai, E.; Zilges, A.; Zolnai, L

    2003-05-19

    Complete angular distributions for the reactions {sup 112,124}Sn({alpha},{alpha}){sup 112,124}Sn have been measured at different energies around the Coulomb barrier. Preliminary results for the {sup 112}Sn x {alpha} and {sup 124}Sn x {alpha} potentials at the energy E{sub c.m.} {approx} 19 MeV are presented. The full determination of the a-nucleus potential for both nuclides may also help to understand the behaviour of {alpha}-nucleus potentials along an isotopic chain.

  12. Effect of cell-surface components and metabolites of lactic acid bacteria and probiotic organisms on cytokine production and induction of CD25 expression in human peripheral mononuclear cells.

    Science.gov (United States)

    Ashraf, R; Vasiljevic, T; Smith, S C; Donkor, O N

    2014-05-01

    In the current study, the relative contribution of cell-surface components (CSC) and cell-free supernatants (CFS) in the immuno-modulatory properties of 17 strains of probiotic and lactic acid bacteria (LAB) was assessed. The production of pro- and antiinflammatory cytokines including IL-2, IL-4, IL-10, IL-12 p70, IFN-γ, tumor necrosis factor-α (TNF-α), and transforming growth factor-β was measured at different time points after stimulation of buffy coat derived-peripheral blood mononuclear cells (PBMC) from healthy donors with CSC and CFS of probiotic and LAB. Results showed that CSC of probiotic and LAB strains induced production of T helper 1 and 2 type cytokines. Transforming growth factor-β was stimulated at highest concentrations, followed by IL-10 and TNF-α. The CFS of all tested bacterial strains induced PBMC for significantly high levels of IL-10 secretion compared with unstimulated cells, but the values were less than lipopolysaccharide-stimulated cells. Cytokines due to CFS stimulation showed declined concentration for IL-2, TNF-α, and IL-4, and complete disappearance of IL-12, IFN-γ, and transforming growth factor-β in the cultured medium at 96 h of incubation. Results of cytokine data demonstrate proinflammatory TNF-α immune responses are mainly directed through cell-surface structures of probiotic and LAB, but antiinflammatory immune responses are mediated both by metabolites and cell-surfaces of these bacteria. The induction of CD4(+)CD25(+) regulatory T cells after stimulation of PBMC with CSC and CFS of probiotic and LAB showed regulatory T cell activity appeared to be influenced both by the CSC and metabolites, but was principally triggered by cell surfaces of probiotic and LAB strains.

  13. Early changes of CD4+CD25+Foxp3+ regulatory T cells and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qin; LU Yuan-qiang; JIANG Jiu-kun; GU Lin-hui; MOU Han-zhou

    2012-01-01

    Background Hemorrhagic shock induces immune dysfunction.Regulatory T cells (Tregs),T-helper (Th) cells,and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses.This study was conducted to investigate the early pathophysiological changes of CD4+CD25+Foxp3+ Treg and Th1/Th2,Tc1/Tc2profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation. Methods A rat model of controlled hemorrhagic shock with no fluid resuscitation was established.Peripheral blood samples were taken before and four hours after hemorrhagic shock with no fluid resuscitation.Three color flow cytometry was used to detect Tregs,Th1,Th2,Tc1 and Tc2 cells in the samples.Results In the peripheral blood of rats,the percentage of Tregs four hours after hemorrhagic shock was significantly lower than before hemorrhagic shock (P=0.001).The ratios of Th1/Th2 and Tc1/Tc2 were changed from (23.08±8.98)%to (23.91±15.36)%,and from (40.40:1:21.56)% to (65.48±23.88)%,respectively.Conclusions At an eady stage,the advent of hemorrhagic shock is related to an early decrease of Tregs,and a mild shift in the Th1/Th2,Tc1/Tc2 balance toward Th1 and Tc1 dominance.These changes are part of a hyper-inflammatory state of the host,and will deteriorate the maintenance of immune balance.Further influences and detailed mechanisms need to be investigated.

  14. 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.

  15. 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.

  16. 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.

  17. Hb Bronte or alpha93(FG5)Val-->Gly: a new unstable variant of the alpha2-globin gene, associated with a mild alpha(+)-thalassemia phenotype.

    Science.gov (United States)

    Lacerra, Giuseppina; Testa, Rosario; De Angioletti, Maria; Schilirò, Gino; Carestia, Clementina

    2003-08-01

    We report a new unstable variant identified in three carriers of a family from East Sicily; it was named Hb Bronte after the place from which the family originated. DNA sequencing from nucleotides -181 to +894 (alpha1) and to +884 (alpha2) revealed a GTG-->GGG substitution at codon 93 of the alpha2-globin gene. The MCV and MCH values were at the lower end of the normal range in the carriers. On cation exchange high performance liquid chromatography (HPLC), the Hb A2 level was apparently increased to around 6%, and a small abnormal peak (0.3-0.4%) was detected after Hb A2. Two abnormal bands were detected by cellulose acetate electrophoresis: a major band (about 3-4%) migrated between Hb A and Hb F; a minor band (<1%) migrated between Hb A2 and carbonic anhydrase. Normal values of Hb A2 were detected by DEAE microchromatography. On reversed phase HPLC the variant chain was not detected, and most likely it was eluted with the alpha chain peak. The isopropanol stability test was very slightly positive in the carriers. Hemolytic symptoms were absent with the exception of indirect bilirubin, which was at high borderline in 2/3 carriers. In biosynthesis in vitro, the specific activity of the alpha chains was much higher than that of the beta-globin chains, and the alpha/beta biosynthetic ratio in the mother and proband was of the beta-thalassemia (thal) type (2.24 and 2.54, respectively). Time course experiments showed that the increase of the 3H-specific activity of the peak containing normal and variant alpha chains was not linear and was much higher than that of beta chains; moreover, the alpha/beta biosynthetic ratio varied during the 2 hours incubation.

  18. The QSE-reduced $\\alpha$ Network

    CERN Document Server

    Hix, W R; Wheeler, J C; Thielemann, F K

    1998-01-01

    Examination of the process of silicon burning, the burning stage that leads to the production of the iron peak nuclei, reveals that the nuclear evolution is dominated by large groups of nuclei in mutual equilibrium. These quasi-equilibrium (QSE) groups form well in advance of the global Nuclear Statistical Equilibrium (NSE). We present an improved ``minimal'' nuclear network, which takes advantage of quasi-equilibrium in order to calculate the nuclear evolution and energy generation while further reducing the computational cost compared to a conventional \\alpha-chain network. During silicon burning, the resultant \\emph{QSE-reduced} \\alpha network is twice as fast as the full \\alpha network it replaces and requires the tracking of only half as many abundance variables, without significant loss of accuracy. When the QSE-reduced \\alpha network is used in combination with a conventional an accurate approximation for all of the burning stages from He burning to NSE, while tracking only 7 abundances. These reductio...

  19. 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

  20. 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.

  1. 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.

  2. Effect of low electric fields on alpha scintillation light yield in liquid argon

    Energy Technology Data Exchange (ETDEWEB)

    Agnes, P.; Albuquerque, I. F. M.; 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.; Cecco, S. De; Deo, M. De; Vincenzi, M. De; Derbin, A.; Devoto, A.; Eusanio, F. Di; Pietro, G. Di; 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.

    2017-01-01

    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 2% increase in light yield compared to alphas in no field.

  3. The role of regulatory T lymphocyte in human immunodeficiency syndrome%CD4+CD25+调节性T细胞与人类获得性免疫缺陷病毒感染关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    贺琼; 徐赫; 杜桂书; 邓路瑶; 吴利洋; 徐兰; 王月丹

    2007-01-01

    CD4+CD25+调节性T细胞,是调节性T细胞中功能最重要的一类.它是一类具有特殊免疫调节功能的T细胞亚群.它能够抑制自身免疫病的发生和发展,参与肿瘤免疫的调节,同时在感染和移植免疫中也发挥着极其重要的作用.T细胞的这一亚群具有免疫调节和免疫抑制的特性,新近发现它亦与艾滋病的发生、发展关系密切.HIV进入人体后,CD4+CD25+调节性T细胞抑制了机体的免疫效应但它也同时被感染,最终由于细胞毒的作用而死亡.由于调节性T细胞数量的减少不能有效地发挥其抑制作用,HIV持续的过度活化使得T细胞逐渐耗竭说明在HIV发生、发展的不同阶段Treg细胞可能都发挥了免疫抑制作用.但是却对HIV感染与艾滋病发病的进程产生了不同的效应.此外,CD4+CD25+调节性T细胞还与HIV病毒的持续存在密切相关.本文就CD4+CD25+调节性T细胞与人类获得性免疫缺陷病毒(HIV)感染之间关系进行初步的探讨.

  4. 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...

  5. Branched-chain fatty acid biosynthesis in a branched-chain amino acid aminotransferase mutant of Staphylococcus carnosus

    DEFF Research Database (Denmark)

    Beck, Hans Christian

    2005-01-01

    Fatty acid biosynthesis by a mutant strain of Staphylococcus carnosus deficient in branched-chain amino acid aminotransferase (IlvE) activity was analysed. This mutant was unable to produce the appropriate branched-chain alpha-ketoacid precursors for branched-chain fatty acid biosynthesis from...... for 2-methylpropanoic acid production, revealing that the IlvE protein plays an important, but not essential role in the biosynthesis of branched-chain fatty acids and secondary metabolites in S. carnosus....

  6. Maximal right smooth extension chains

    CERN Document Server

    Huang, Yun Bao

    2010-01-01

    If $w=u\\alpha$ for $\\alpha\\in \\Sigma=\\{1,2\\}$ and $u\\in \\Sigma^*$, then $w$ is said to be a \\textit{simple right extension}of $u$ and denoted by $u\\prec w$. Let $k$ be a positive integer and $P^k(\\epsilon)$ denote the set of all $C^\\infty$-words of height $k$. Set $u_{1},\\,u_{2},..., u_{m}\\in P^{k}(\\epsilon)$, if $u_{1}\\prec u_{2}\\prec ...\\prec u_{m}$ and there is no element $v$ of $P^{k}(\\epsilon)$ such that $v\\prec u_{1}\\text{or} u_{m}\\prec v$, then $u_{1}\\prec u_{2}\\prec...\\prec u_{m}$ is said to be a \\textit{maximal right smooth extension (MRSE) chains}of height $k$. In this paper, we show that \\textit{MRSE} chains of height $k$ constitutes a partition of smooth words of height $k$ and give the formula of the number of \\textit{MRSE} chains of height $k$ for each positive integer $k$. Moreover, since there exist the minimal height $h_1$ and maximal height $h_2$ of smooth words of length $n$ for each positive integer $n$, we find that \\textit{MRSE} chains of heights $h_1-1$ and $h_2+1$ are good candidates t...

  7. The C-terminal region of laminin beta chains modulates the integrin binding affinities of laminins.

    Science.gov (United States)

    Taniguchi, Yukimasa; Ido, Hiroyuki; Sanzen, Noriko; Hayashi, Maria; Sato-Nishiuchi, Ryoko; Futaki, Sugiko; Sekiguchi, Kiyotoshi

    2009-03-20

    Laminins are major cell-adhesive proteins in basement membranes that are capable of binding to integrins. Laminins consist of three chains (alpha, beta, and gamma), in which three laminin globular modules in the alpha chain and the Glu residue in the C-terminal tail of the gamma chain have been shown to be prerequisites for binding to integrins. However, it remains unknown whether any part of the beta chain is involved in laminin-integrin interactions. We compared the binding affinities of pairs of laminin isoforms containing the beta1 or beta2 chain toward a panel of laminin-binding integrins, and we found that beta2 chain-containing laminins (beta2-laminins) bound more avidly to alpha3beta1 and alpha7X2beta1 integrins than beta1 chain-containing laminins (beta1-laminins), whereas alpha6beta1, alpha6beta4, and alpha7X1beta1 integrins did not show any preference toward beta2-laminins. Because alpha3beta1 contains the "X2-type" variable region in the alpha3 subunit and alpha6beta1 and alpha6beta4 contain the "X1-type" region in the alpha6 subunit, we hypothesized that only integrins containing the X2-type region were capable of discriminating between beta1-laminins and beta2-laminins. In support of this possibility, a putative X2-type variant of alpha6beta1 was produced and found to bind preferentially to beta2-laminins. Production of a series of swap mutants between the beta1 and beta2 chains revealed that the C-terminal 20 amino acids in the coiled-coil domain were responsible for the enhanced integrin binding by beta2-laminins. Taken together, the results provide evidence that the C-terminal region of beta chains is involved in laminin recognition by integrins and modulates the binding affinities of laminins toward X2-type integrins.

  8. 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

  9. 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

  10. [The treatment by expanded ex vivo autologous regulatory T-cells CD4+CD25+FoxP3+CD127low restores the balance of immune system in patients with remitting-relapsing multiple sclerosis].

    Science.gov (United States)

    Eliseeva, D D; Lifshits, G V; Lokhonina, A V; Zhdanov, D D; Zavalishin, I A; Bykovskaya, S N

    2016-01-01

    Цель исследования — оценка клинической эффективности и безопасности аутологичных (собственных) Трег-клеток — CD4+CD25+Foxp3+CD127low, выделенных из крови больных ремиттирующим рассеянным склерозом (РРС). Больные аутоиммунными заболеваниями имеют сниженное число и нарушенную супрессорную функцию циркулирующих в крови периферических Трег. С целью коррекции дефекта периферических Трег можно выделить клетки-предшественники, культивировать вне организма (ex vivo) больного и ввести увеличенное количество аутологичных (собственных) Трег в виде вакцины Трег. Материал и методы. Была разработана методика культивирования ex vivo, с помощью которой количество Трег можно увеличить в 30—40 раз в течение 5—7 дней. Выращенные ex vivo клетки состоят более чем из 90% CD4+CD25+Foxp3+CD127low Трег и обладают высоким уровнем супрессорной активности. В пилотные испытания были включены 14 больных РРС, которым подкожно были введены выращенные ex vivo Трег в дозе от 2,8 до 4,5·108 клеток на одну инъекцию. Длительность наблюдения за больными составила 1 год. Результаты и обсуждение. Уровень Трег в крови этих больных повысился в 1,5—2

  11. Introduction of the human pro. cap alpha. 1(I) collagen gene into pro. cap alpha. 1(I)-deficient Mov-13 mouse cells leads to formation of functional mouse-human hybrid type I collagen

    Energy Technology Data Exchange (ETDEWEB)

    Schnieke, A.; Dziadek, M.; Bateman, J.; Mascara, T.; Harbers, K.; Gelinas, R.; Jaenisch, R.

    1987-02-01

    The Mov-13 mouse strain carries a retroviral insertion in the pro..cap alpha..1(I) collagen gene that prevents transcription of the gene. Cell lines derived from homozygous embryos do not express type I collagen although normal amounts of pro..cap alpha..2 mRNA are synthesized. The authors have introduced genomic clones of either the human or mouse pro..cap alpha..1(I) collagen gene into homozygous cell lines to assess whether the human or mouse pro..cap alpha..1(I) chains can associate with the endogenous mouse pro..cap alpha..2(I) chain to form stable type I collagen. The human gene under control of the simian virus 40 promoter was efficiently transcribed in the transfected cells. Protein analyses revealed that stable heterotrimers consisting of two human ..cap alpha..1 chains and one mouse ..cap alpha..2 chain were formed and that type I collagen was secreted by the transfected cells at normal rates. However, the electrophoretic migration of both ..cap alpha..1(I) and ..cap alpha..2(I) chains in the human-mouse hybrid molecules were retarded, compared to the ..cap alpha..(I) chains in control mouse cells. Inhibition of the posttranslational hydroxylation of lysine and proline resulted in comigration of human and mouse ..cap alpha..1 and ..cap alpha..2 chains, suggesting that increased posttranslational modification caused the altered electrophoretic migration in the human-mouse hybrid molecules. Amino acid sequence differences between the mouse and human ..cap alpha.. chains may interfere with the normal rate of helix formation and increase the degree of posttranslational modifications similar to those observed in patients with lethal perinatal osteogenesis imperfecta. The Mov-13 mouse system should allow the authors to study the effect specific mutations introduced in transfected pro..cap alpha..1(I) genes have on the synthesis, assembly, and function of collagen I.

  12. The determination of $\\alpha_s$ by the ALPHA collaboration

    CERN Document Server

    Bruno, Mattia; Fritzsch, Patrick; Korzec, Tomasz; Ramos, Alberto; Schaefer, Stefan; Simma, Hubert; Sint, Stefan; Sommer, Rainer

    2016-01-01

    We review the ALPHA collaboration strategy for obtaining the QCD coupling at high scale. In the three-flavor effective theory it avoids the use of perturbation theory at $\\alpha > 0.2$ and at the same time has the physical scales small compared to the cutoff $1/a$ in all stages of the computation. The result $\\Lambda_\\overline{MS}^{(3)}=332(14)$~MeV is translated to $\\alpha_\\overline{MS}(m_Z)=0.1179(10)(2)$ by use of (high order) perturbative relations between the effective theory couplings at the charm and beauty quark "thresholds". The error of this perturbative step is discussed and estimated as $0.0002$.

  13. The changes of cardiopulmonary function and the correlation with the ratios of regulatory T cells in OA rats%骨关节炎大鼠心、肺功能变化与CD4+ CD25+ Foxp3+ Treg的相关性分析

    Institute of Scientific and Technical Information of China (English)

    程园园; 刘健; 冯云霞; 刘磊; 万磊

    2013-01-01

    Objective:To observe the changes of cardiopulmonary function and expression of CD4 + CD25+ Foxp3+ Treg in Os-teoarthritis ( OA) rats, thus to explore the role that CD4+ CD25 + Foxp3 + Treg played in decline of cardiopulmonary of OA rats. Methods: 20 rats were randomly divided into 2 groups; normal group( NC) and model group( NC) , 10 in each group. Rats in MC group were induced to OA model by injecting papain and L-cystine into right knee joint. Cartilage lesions were scored by the modified Mankin Scale; cardiac function was detected by ultrasonography; pulmonary function was detected by spirometry; interleukin (IL) -17 ,4 were evaluated by ELJSA; the ratios of CD4+ CD25 + Foxp3 + Treg in peripheral blood were measured by Flow cytometry. Results: Compared to NC group, Mankin scores in MC group were significantly increased; part of parameters of cardiopulmonary function were obviously changed, and accounts for 60% and 20% of the selected indexes respectively; expression of IL-17 was significantly ascend, expression of IL-4 and CD4 + CD25+ Foxp3 + Treg were significantly descend ( P < 0. 01 or P < 0. 05 ). Conclusion: While articular cartilage lesions occurred in OA rats, cardiopulmonary function and the expression of peripheral CD4 + CD25 + Foxp3+ Treg were also declined, and significantly correlated with Mankin scores, expression of IL-17,IL-4, suggesting that immune imbalance and aggravated inflammatory due to attenuated regulatory effect of regulatory T cells (Treg) , result in joint, cardiac and pulmonary injury, finally causing cardiopulmonary function declined.%目的:通过观察骨关节炎(Osteoarthritis,OA)大鼠、心肺功能的变化,及其与外周血CD4+CD25+Foxp3+Treg表达量变化,探讨骨关节炎中心、肺功能的异常与CD4+CD25+Foxp3+Treg的关系.方法:20只大鼠随机分为正常对照组(NC)和模型对照组(MC),每组各10只.MC组大鼠采用关节腔注射木瓜蛋白酶(Papain)和L-半胱氨酸(L-cystine)方法制成骨关节炎

  14. Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice

    DEFF Research Database (Denmark)

    Guo, L T; Zhang, X U; Kuang, W;

    2003-01-01

    Deficiency of laminin alpha2 is the cause of one of the most severe muscular dystrophies in humans and other species. It is not yet clear how particular mutations in the laminin alpha2 chain gene affect protein expression, and how abnormal levels or structure of the protein affect disease. Animal...... models may be valuable for such genotype-phenotype analysis and for determining mechanism of disease as well as function of laminin. Here, we have analyzed protein expression in three lines of mice with mutations in the laminin alpha2 chain gene and in two lines of transgenic mice overexpressing...... the human laminin alpha2 chain gene in skeletal muscle. The dy(3K)/dy(3K) experimental mutant mice are completely deficient in laminin alpha2; the dy/dy spontaneous mutant mice have small amounts of apparently normal laminin; and the dy(W)/dy(W) mice express even smaller amounts of a truncated laminin alpha...

  15. Biosynthesis of Tcr-alpha, beta and Tcr-gamma, delta/CD3 complexes

    DEFF Research Database (Denmark)

    Bauguil-Caspar, S; Arnaud, J; Kuhlmann, J;

    1993-01-01

    Jurkat J76 clone, LYON L12.37 clone and L12.37 cells transfected with J76-alpha cDNA or J76 Tcr-alpha mutated cDNA (J79) were analysed for membrane expression of Tcr/CD3 complex using WT31 mAb (Tcr-alpha, beta) or Tcr-delta 1 mAb (Tcr-gamma, delta): LYON cells express V beta 9 bearing Tcr-beta...... chains. J76 Tcr-alpha cDNA transfected LYON cells have intracellular Tcr-gamma, delta chains and J79 Tcr-alpha cDNA transfected LYON cells have intracellular Tcr-alpha (M), beta chains....

  16. New ALPHA-2 magnet

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    On 21 June, members of the ALPHA collaboration celebrated the handover of the first solenoid designed for the ALPHA-2 experiment. The magnet has since been successfully installed and is working well.   Khalid Mansoor, Sumera Yamin and Jeffrey Hangst in front of the new ALPHA-2 solenoid. “This was the first of three identical solenoids that will be installed between now and September, as the rest of the ALPHA-2 device is installed and commissioned,” explains ALPHA spokesperson Jeffrey Hangst. “These magnets are designed to allow us to transfer particles - antiprotons, electrons and positrons - between various parts of the new ALPHA-2 device by controlling the transverse size of the particle bunch that is being transferred.” Sumera Yamin and Khalid Mansoor, two Pakistani scientists from the National Centre for Physics in Islamabad, came to CERN in February specifically to design and manufacture these magnets. “We had the chance to work on act...

  17. Lyman Alpha Control

    CERN Document Server

    Nielsen, Daniel Stefaniak

    2015-01-01

    This document gives an overview of how to operate the Lyman Alpha Control application written in LabVIEW along with things to watch out for. Overview of the LabVIEW code itself as well as the physical wiring of and connections from/to the NI PCI-6229 DAQ box is also included. The Lyman Alpha Control application is the interface between the ALPHA sequencer and the HighFinesse Wavelength Meter as well as the Lyman Alpha laser setup. The application measures the wavelength of the output light from the Lyman Alpha cavity through the Wavelength Meter. The application can use the Wavelength Meter’s PID capabilities to stabilize the Lyman Alpha laser output as well as switch between up to three frequencies.

  18. Interpreting EEG alpha activity.

    Science.gov (United States)

    Bazanova, O M; Vernon, D

    2014-07-01

    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  19. Alpha Shapes and Proteins

    DEFF Research Database (Denmark)

    Winter, Pawel; Sterner, Henrik; Sterner, Peter

    2009-01-01

    We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

  20. A cis-proline in alpha-hemoglobin stabilizing protein directs the structural reorganization of alpha-hemoglobin.

    Science.gov (United States)

    Gell, David A; Feng, Liang; Zhou, Suiping; Jeffrey, Philip D; Bendak, Katerina; Gow, Andrew; Weiss, Mitchell J; Shi, Yigong; Mackay, Joel P

    2009-10-23

    alpha-Hemoglobin (alphaHb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with alphaHb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting alphaHb to a conformation in which the heme is coordinated at both axial positions by histidine side chains (bis-histidyl coordination). Currently, the detailed mechanism by which AHSP induces structural changes in alphaHb has not been determined. Here, we present x-ray crystallography, NMR spectroscopy, and mutagenesis data that identify, for the first time, the importance of an evolutionarily conserved proline, Pro(30), in loop 1 of AHSP. Mutation of Pro(30) to a variety of residue types results in reduced ability to convert alphaHb. In complex with alphaHb, AHSP Pro(30) adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in alphaHb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the alphaHb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of alphaHb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops.

  1. Solitons and 1/f Noise in Molecular Chains

    CERN Document Server

    Rosu, H C

    1993-01-01

    Davydov's model of solitons in alpha-helix protein chains is shown to display features of self-organized criticality (SOC), i.e., power law behaviour of correlations in space and 1/f-noise, as a consequence of considering random peptide group displacements from their (periodic) equilibrium positions along a chain. This may shed light on a basic mechanism leading to obtain flicker noise in alpha-helix protein chains and to predict a SOC regime in biomolecular structures from first principles. We believe our treatment of 1/f noise to be of some relevance to recent findings due to Voss on DNA [Phys. Rev. Lett. 68, 3805 (1992)].

  2. 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...

  3. Laser assisted {alpha} decay

    Energy Technology Data Exchange (ETDEWEB)

    Castaneda Cortes, Hector Mauricio

    2012-02-01

    Excited or short-lived nuclei often decay by emitting alpha particles that are assumed to be preformed inside the nucleus and confined in the nuclear potential well. In this picture, {alpha} decay refers to the tunneling of the alpha particle through the potential barrier. In this thesis we investigate for the first time how strong laser fields can assist the tunneling of the alpha particle and thus influence the nuclear decay. Generally speaking, laser-assisted {alpha} decay can be described as laser-assisted tunneling of a quasistationary state, i.e, a slowly decaying state. Our theoretical treatment is developed starting from the complex trajectory formulation of the well-known strong-field approximation used to describe laser-induced ionization. We extend this formulation and develop a method to treat the decay of quasistationary states. The effect of both static and optical and X-ray monochromatic fields on the lifetimes and {alpha}-particle emission spectra are investigated for a number of {alpha}-emitting nuclei. We find that even at strong intensities, the laser-induced acceleration of the {alpha} decay is negligible, ranging from a relative modification in the decay rate of 10{sup -3} for static fields of electric field strengths of 10{sup 15} V/m, to 10{sup -8} for strong optical fields with intensities of 10{sup 22} W/cm{sup 2}, and to 10{sup -6} for strong X-ray fields with laser intensities around 10{sup 24} W/cm{sup 2}. However, the effect of the external field is visible in the spectrum of emitted alpha particles, leading in the case of optical fields even to rescattering phenomena for intensities approaching 6 x 10{sup 22} W/cm{sup 2}. The dynamics of the alpha particle in laser fields of intensities below the rescattering limit is investigated.

  4. Predictions on the alpha decay half lives of Superheavy nuclei with Z = 113 in the range 255 l.e. A l.e. 314

    CERN Document Server

    Santhosh, K P; Nithya, C; Priyanka, B

    2016-01-01

    An intense study of the alpha decay properties of the isotopes of superheavy element Z=113 have been performed within the Coulomb and proximity potential model for deformed nuclei (CPPMDN) within the wide range 255 l.e. A l.e. 314. The predicted alpha decay half lives of $^{278}$113 and $^{282}$113 and the alpha half lives of their decay products are in good agreement with the experimental data. 6{\\alpha) chains and 4{\\alpha} chains predicted respectively for $^{278}$113 and $^{282}$113 are in agreement with the experimental observation. Our study shows that the isotopes in the mass range 278 l.e. A l.e. 286 will survive fission and can be synthesized and detected in the laboratory via alpha decay. In our study, we have predicted 6{\\alpha} chains from $^{279}$113, 4{\\alpha} chains from $^{286}$113, 3{\\alpha} chains from $^{280,281,283}$113, 2{\\alpha} chains from $^{284}$113 and 1{\\alpha} chain from $^{285}$113. We hope that these predictions will be a guideline for future experimental investigations.

  5. alpha-thalassemia mutations in Khuzestan Province, Southwest Iran.

    Science.gov (United States)

    Zandian, Khodamorad; Nateghi, Jamal; Keikhaie, Bijan; Pedram, Mohammad; Hafezi-Nejad, Nima; Hadavi, Valeh; Oberkanins, Christian; Azarkeivan, Azita; Law, Hai-Yang; Najmabadi, Hossein

    2008-01-01

    Although alpha-thalassemia (alpha-thal) is the most common hereditary hemoglobin (Hb) disorder in Iran, no comprehensive data are so far available on the prevalence of the disease in the province of Khuzestan in Southwest Iran. This study investigates the spectrum of alpha-thal mutations in this region. One hundred and twenty-one subjects from Khuzestan Province, Iran, were initially tested for the three most common Iranian alpha-thal mutations (- alpha3.7, -alpha4.2, and --MED) by gap-polymerase chain reaction (gap-PCR). Reverse hybridization test strips and DNA sequencing were used to identify additional alpha-globin mutations. A total of 131 mutated alpha-globin alleles were identified in these patients. Of the 13 mutations that were detected in Khuzestan Province, Iran, the - alpha3.7 single gene deletion was the most frequently identified variant, representing 62.6% of the total; we also observed significant numbers of individuals with compound heterozygous mutations. On the basis of our results, we strongly recommend screening for the most common mutations to improve the molecular diagnosis of anemia in this region.

  6. Genetics Home Reference: alpha thalassemia

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions alpha thalassemia alpha thalassemia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Alpha thalassemia is a blood disorder that reduces the production ...

  7. The role of CD4+ CD25+ Foxp3+ Treg in the immune tolerance induced by portal vein injection of donor splenocytes%门静脉输注供者脾细胞诱导的供者特异性免疫低反应性

    Institute of Scientific and Technical Information of China (English)

    徐胜元; 何凡; 吴敏; 蔡明; 丁召; 郑翔; 陈知水

    2009-01-01

    目的 探讨经门静脉输注供者脾细胞能否