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Regulatory T Cells (regulatory t + cell)
Kinds of Regulatory T Cells Terms modified by Regulatory T Cells Selected AbstractsRegulatory T cells in human disease and their potential for therapeutic manipulationIMMUNOLOGY, Issue 1 2006Leonie S. Taams Summary Regulatory T cells are proposed to play a central role in the maintenance of immunological tolerance in the periphery, and studies in many animal models demonstrate their capacity to inhibit inflammatory pathologies in vivo. At a recent meeting [Clinical Application of Regulatory T Cells, 7,8 April 2005, Horsham, UK, organized by the authors of this review, in collaboration with the British Society for Immunology and Novartis] evidence was discussed that certain human autoimmune, infectious and allergic diseases are associated with impaired regulatory T-cell function. In contrast, evidence from several human cancer studies and some infections indicates that regulatory T cells may impair the development of protective immunity. Importantly, certain therapies, both those that act non-specifically to reduce inflammation and antigen-specific immunotherapies, may induce or enhance regulatory T-cell function. The purpose of this review was to summarize current knowledge on regulatory T-cell function in human disease, and to assess critically how this can be tailored to suit the therapeutic manipulation of immunity. [source] Regulatory T Cells in children with intestinal parasite infectionPARASITE IMMUNOLOGY, Issue 10 2009M. H. GARCÍA-HERNÁNDEZ Summary Chronic intestinal parasite infection can induce both persistent immune activation and defective responsiveness of T cells. This study aimed to assess the number and function of T regulatory (Treg) cells in children with intestinal parasite infection. We have studied the peripheral blood from 93 children, 53 of them parasitized with protozoa, helminths, or both; the remainder were non parasitized, healthy controls. The number and function of CD4+ CD25high and CD4+ Foxp3+ cells were similar in parasitized and control children. In contrast, there was a significant increase in the levels of CD3+ CD69+, CD4+ CTLA-4+, and CD8+ CD28, T cells in helminth infected children. Moreover, some of these patients showed a diminished response to CD3/CD28 stimulation in comparison with the control children. Our data strongly suggest that whilst Treg cells are not affected by intestinal parasite infection, CD3+ CD69+, CD4+ CTLA-4+ and CD8+ CD28, lymphocytes may play an important, but as yet undetermined role in the diminished immune competence observed in parasitized children. [source] REVIEW ARTICLE: Regulatory T Cells and Their Role in PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Anne Leber Citation Leber A, Teles A, Zenclussen AC. Regulatory T cells and their role in pregnancy. Am J Reprod Immunol 2010 Regulatory T cells emerge in the last years as key players in allowing fetal survival within the maternal uterus. They were shown to be a unique subpopulation of T cells expanding during human and murine pregnancy. The importance of Treg for a normal pregnancy situation was proven by studies showing that their absence impairs murine pregnancy while the adoptive transfer of Treg prevents fetal rejection. In humans, pregnancy pathologies are associated with lower Treg frequencies while therapies that improve pregnancy outcome are able to boost their number. Functional studies have shown that Treg can regulate immune cell responses directly at the fetal,maternal interface either by interacting with other cells or by inducing the expression of immune regulatory molecules. This article revises relevant literature on regulatory T cells in human and murine pregnancy. [source] ORIGINAL ARTICLE: PD-1 but not CTLA-4 Blockage Abrogates the Protective Effect of Regulatory T Cells in a Pregnancy Murine ModelAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009Paul Ojiambo Wafula Problem, Regulatory T cells (Treg) play an important role in fetal protection. They expand during normal pregnancy and protect paternal/fetal antigens from rejection by maternal effector cells. Accordingly, the transfer of Treg obtained from BALB/c-mated CBA/J females prevents abortion in DBA/2J-mated animals. The actual mechanism through which Treg mediate their protective effect is still inconclusive. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and Programmed cell death 1 (PD-1) are some of known Treg-associated molecules; however, their role in Treg-mediated fetal protection in murine model has not been investigated. Method of study, Treg obtained from normal pregnant animals (NP; CBA/J × BALB/c) on day 14 were adoptively transferred into abortion-prone mice (AP; CBA/J × DBA/2J) intravenously on day 2 of pregnancy. An amount of 250 ,g of either anti-PD-1 or anti-CTLA-4 mAb were injected intraperitoneally on days 0, 3, 6 and 9 of pregnancy. Controls received Treg + IgG or Treg + PBS. NP or AP treated with PBS served as additional controls. Results, Blocking PD-1 abrogated the protective effect of Treg, resulting in a higher median abortion rate in comparison with the Treg/isotype-treated control while CTLA-4 blockage did not interfere with the protective effect of Treg. This was associated with a diminished number of vascular endothelial growth factor-A+ cells, previously reported as stimulators of lymphocyte extravasation in preterm labor. Conclusion, Our data suggest PD-1 as an important mediator in Treg-induced fetal protection in the CBA/J × DBA/2J murine model. [source] ORIGINAL ARTICLE: Changes in the Subpopulation of CD25+ CD4+ and FOXP3+ Regulatory T Cells in Decidua with Respect to the Progression of Labor at Term and the Lack of Analogical Changes in the Subpopulation of Suppressive B7-H4+ Macrophages , A Preliminary ReportAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Krystyna Galazka Problem, The initiation of labor is accompanied by alterations in the level of maternal immune tolerance toward fetal antigens. It is a complex molecular response leading to a brief activation of the maternal immune system with an accompanying capacity to restrict this same activation. The aim of our study was to evaluate the subpopulation of regulatory T cells (Tregs) and B7-H4 macrophages in the decidua basalis during cesarean sections performed on patients in various stages of labor. Method of study, The decidual tissue samples evaluated in our study were obtained from 23 pregnant women who underwent cesarean sections at term. Moreover, the patients were divided into three subgroups according to the progression of labor at the time of the cesarean. The presence of Treg cells and B7-H4 positive macrophages were analysed by fluorescence-activated cell sorter. Results, The percentages of FOXP3+ cells in the subpopulation of CD25+ CD4+ T lymphocytes found in the deciduas of patients decreased with the successive stages of labor, while the percentages of B7-H4 positive cells in the macrophage subpopulation remained almost constant. Conclusion, These changes in the Treg cell subpopulation in the decidua would seem to be related to a brief activation of the maternal immune system as labor begins and lack of analogical changes in the subpopulation of decidual suppressive B7-H4+ macrophages that enable the restriction of this same activation as labor progresses. [source] Tolerance Signaling Molecules and Pregnancy: IDO, Galectins, and the Renaissance of Regulatory T CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2007Peter Terness Problem, Is the concept of maternal tolerance preventing rejection of the semi-allogeneic ,fetal allograft' still valid? Method of study, Compilation of expert reviews of literature and recent advances in research on indoleamine-2,3 dioxygenase (IDO), regulatory T cells and galectin-1. Results and Conclusion, A role for IDO in pregnancy success remains speculative, but solid data exist to support a role for Treg cells, and for galectin-1 in induction and action of Treg cells. Just as several signals may need to be simultaneously present to induce Th1 cytokine-triggered abortions, more than 1 signal may need to be simultaneously present to prevent rejection and ensure success. Both complement and coagulation pathways appear necessary for embryo execution. [source] Regulatory T Cells Are Critical to Tolerance Induction in Presensitized Mouse Transplant Recipients Through Targeting Memory T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010W. Ge Memory T cells are a significant barrier to induction of transplant tolerance. However, reliable means to target alloreactive memory T cells have remained elusive. In this study, presensitization of BALB/c mice with C57BL/6 skin grafts generated a large number of OX40+CD44hieffector/memory T cells and resulted in rapid rejection of donor heart allografts. Recognizing that anti-OX40L monoclonal antibody (mAb) (,-OX40L) monotherapy prolonged graft survival through inhibition and apoptosis of memory T cells in presensitized recipients, ,-OX40L was added to the combined treatment protocol of LF15,0195 (LF) and anti-CD45RB (,-CD45RB) mAb,a protocol that induced heart allograft tolerance in non-presensitized recipients but failed to induce tolerance in presensitized recipients. Interestingly, this triple therapy restored donor-specific heart allograft tolerance in our presensitized model that was associated with induction of tolerogenic dendritic cells and CD4+CD25+Foxp3+ T regulatory cells (Tregs). Of note, CD25+ T cell depletion in triple therapy recipients prevented establishment of allograft tolerance. In addition, adoptive transfer of donor-primed effector/memory T cells into tolerant recipients markedly reduced levels of Tregs and broke tolerance. Our findings indicated that targeting memory T cells, by blocking OX40 costimulation in presensitized recipients was very important to expansion of Tregs, which proved critical to development of tolerance. [source] The Jak Inhibitor CP-690,550 Preserves the Function of CD4+CD25brightFoxP3+ Regulatory T Cells and Inhibits Effector T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010V. D. K. D. Sewgobind The Jak inhibitor CP-690,550 inhibits alloreactivity and is currently being investigated for prevention of allograft rejection after transplantation. In this study, we examined the effect of CP-690,550 on IL-2-mediated Jak/STAT5 phosphorylation by CD4+CD25brightFoxP3+CD127,/low T cells (Treg) and CD4+CD25neg effector T cells (Teff) in kidney transplant (KTx) patients. Phosphospecific flow cytometry was used to study the effect of CP-690,550 on IL-2-induced intracellular STAT5-phosphorylation. IL-2-induced phosphorylation of STAT5 (P-STAT5) in both Treg and Teff, which was significantly higher for CD4+CD25bright Treg (increased by 71%, mean) than for CD4+CD25neg Teff (increased by 42%). In the presence of 100 ng/mL CP-690,550, a clinically relevant exposure, IL-2-induced P-STAT5 was partially inhibited in CD4+CD25brightTreg (% inhibition; 51%), while almost completely blocked in Teff (%inhibition; 84%, p = 0.03). The IC50 was 2,3 times higher for Treg (104 ng/mL) than for Teff (40 ng/mL, p = 0.02). In the presence of CP-690,550, Treg exhibited additional suppressive activities on the alloactivated proliferation of Teff (56%, mean). In addition, CD4+CD25bright Treg from KTx-patients receiving CP-690,550 vigorously suppressed the proliferation of Teff (87%, mean). Our findings show that CP-690,550 effectively inhibits Teff function but preserves the suppressive activity of CD4+CD25bright regulatory T cells. [source] IFN-, Triggered STAT1-PKB/AKT Signalling Pathway Influences the Function of Alloantigen Reactive Regulatory T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010B. Wei CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a key role in the induction and maintenance of peripheral tolerance. Rapid and transient production of IFN-, by Tregs from mice tolerized to alloantigen in vivo has been shown to be critical for their regulatory function. This IFN-, has the potential to affect the function of cells present in the same local microenvironment as the Tregs, including the Tregs themselves. Here we investigated the mechanism by which IFN-, produced by Tregs triggered signaling pathways in alloantigen reactive Tregs themselves thereby influencing their function in vivo. We show that IFN-, production and STAT1 activation was increased, while STAT1-dependent PKB/AKT activation was downregulated in alloantigen reactive Tregs. Further, the activation of STAT1 was blocked in IFN-, receptor deficient as well as IFN-,,deficient Tregs, suggesting that IFN-, produced by the alloantigen reactive Tregs might act in an autocrine manner to induce STAT1 activation. Importantly, STAT1-deficient Tregs failed to control allograft rejection in vivo. Overall, these findings suggest that the IFN-,,induced STAT1-PKB/AKT signaling pathway plays a key role in upregulating the ability of alloantigen reactive Tregs to control graft rejection in vivo. [source] Human FOXP3+ Regulatory T Cells in TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009P. Boros CD4+CD25+FOXP3+ suppressive regulatory T cells (Treg) represent a subset of immune regulatory cells. Based on experimental results, Treg have recently been considered as a potential treatment option in several diseases. Compared with murine Treg, human CD4+CD25+FOXP3+ cells are less well characterized and understood, so a thorough understanding of their biology is vital before clinical applications can be initiated. This review summarizes knowledge on generation, phenotypic characteristics and function of human Treg. The possible role of these cells in organ transplantation, as well as interactions between immunosuppression and Treg are also discussed. [source] Purified Eicosapentaenoic Acid Induces Prolonged Survival of Cardiac Allografts and Generates Regulatory T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009D. Iwami Fish oil, which is rich in eicosapentaenoic acid (EPA), has been found to have immunomodulatory effects. We examined whether administration of purified EPA affected survival of fully mismatched murine cardiac allografts. Hearts from C57BL/10 (H-2b) mice were transplanted into CBA (H-2k) recipients treated with one intraperitoneal dose of purified EPA the day of transplantation. Untreated CBA recipients and recipients given 0.1 g/kg of EPA rejected C57BL/10 hearts (median survival time [MST], 8 and 13 days, respectively). With a 1.0 g/kg dose of EPA, graft survival was markedly prolonged (MST >100 days). To determine whether regulatory cells were generated, naïve mice (secondary recipients) underwent adoptive transfer of splenocytes from EPA-treated primary recipients and cardiac allograft transplantation. Adoptive transfer of whole, CD4+ and CD4+CD25+ splenocytes from EPA-treated recipients induced indefinite survival in secondary recipients. Flow cytometry showed that the CD4+CD25+ cells were Foxp3+. In reverse transcriptase-polymerase chain reaction (RT-PCR) studies, the expression of peroxisome proliferator-activated receptor , (PPAR,) mRNA was upregulated by EPA treatment. A PPAR, antagonist abrogated the prolongation of graft survival induced by EPA treatment (MST, 13 days). Thus, in our model, purified EPA induced prolonged survival of fully mismatched cardiac allografts and generated regulatory T cells dependent on PPAR, activation. [source] New Insights into Mechanisms of Spontaneous Liver Transplant Tolerance: The Role of Foxp3-Expressing CD25+CD4+ Regulatory T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2008W. Li Liver allografts in mice are accepted across MHC barriers without requirement for immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we investigated the role of Foxp3-expressing CD25+CD4+ regulatory T cells (Treg) in the induction of murine liver transplant tolerance. Foxp3+CD25+CD4+ T cells were increased in liver grafts and recipient spleens from day 5 to day 100 posttransplantation, associated with enhanced CTLA4 and TGF-, expression and IL-4 production. Depletion of recipient CD25+CD4+ T cells using anti-CD25 mAb (250 ,g/day) induced acute liver allograft rejection. This was associated with a decreased ratio of Foxp3+ Treg: T effector cells, decreased IL-4 and elevated IL-10 and IL-2 production by graft-infiltrating T cells, and reduced apoptotic activity of graft-infiltrating CD4+ and CD8+ T cells in anti-CD25-mAb-treated recipients. Thus, the data suggest that Foxp3+CD25+CD4+Treg are involved in spontaneous acceptance of liver allografts in mice. The ratio of Treg to T effector cells appears to determine liver transplant outcome. CTLA4, IL-4, TGF-, and apoptosis of graft-infiltrating T cells are also associated with liver transplant tolerance and may contribute, at least in part, to the mechanisms of Treg-mediated immune regulation in this model. [source] Role of IFN, in Allograft Tolerance Mediated by CD4+CD25+ Regulatory T Cells by Induction of IDO in Endothelial CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2007P. Thebault Regulatory T cells have been described to specifically accumulate at the site of regulation together with effector T cells and antigen-presenting cells, establishing a state of local immune privilege. However the mechanisms of this interplay remain to be defined. We previously demonstrated, in a fully MHC mismatched rat cardiac allograft combination, that a short-term treatment with a deoxyspergualine analogue, LF15-0195, induces long-term allograft tolerance with a specific expansion of regulatory CD4+CD25+T cells that accumulate within the graft. In this study, we show that following transfer of regulatory CD4+T cells to a secondary irradiated recipient, regulatory CD25+Foxp3+ and CD25+Foxp3, CD4+T cells accumulate at the graft site and induce graft endothelial cell expression of Indoleamine 2, 3-dioxygenase (IDO) by an IFN,-dependent mechanism. Moreover, in vivo transfer of tolerance can be abrogated by blocking IFN, or IDO, and anti-IFN, reduces the survival/expansion of alloantigen-induced regulatory Foxp3+CD4+T cells. Together, our results demonstrate interrelated mechanisms between regulatory CD4+CD25+T cells and the graft endothelial cells in this local immune privilege, and a key role for IFN, and IDO in this process. [source] Sequential Involvement of Two Distinct CD4+ Regulatory T Cells during the Course of Transplantable Tumor Growth and Protection from 3,Methylcholanthrene-induced Tumorigenesis by CD25,depletionCANCER SCIENCE, Issue 8 2002Isao Tawara The involvement of two phenotypically different regulatory T cells in different stages of tumor growth was investigated. Treatment of BALB/c mice with anti-CD25 monoclonal antibody (mAb) (PC61), but not anti-CD4 mAb (GK1.5) before RL male 1 or Meth A inoculation caused tumor rejection. On the other hand, treatment of BALB/c mice with anti-CD4 mAb (GK1.5) but not anti-CD25 mAb (PC61) on day 6 after inoculation of the same tumors caused rejection. The findings suggest that CD4+CD25+ T cells downregulated the rejection response in the early stage of tumor growth. On the other hand, putative CD4+CD25, T cells downregulated the tumor rejection response in the late stage. Both CD4+CD25+ and putative CD4+CD25-T cells appeared to inhibit the efficient generation of cytotoxic T lymphocytes (CTL). The present study also demonstrated that the treatment of BALB/c mice with anti-CD25 mAb (PC61) at 4 or 6 weeks after 3,methylcholanthrene (3,MC) inoculation retarded tumor occurrence and prolonged survival. [source] Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparumEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2010Linda J. Wammes Abstract Chronic helminth infections induce T-cell hyporesponsiveness, which may affect immune responses to other pathogens or to vaccines. This study investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum -parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children's in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD4+CD25hiFOXP3+ T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminth-uninfected groups: Ag-specific proliferative responses increased upon CD4+CD25hi T-cell depletion in geohelminth-infected subjects only. In addition, IFN-, production in response to both BCG and parasitized RBC was increased after removal of CD4+CD25hi T cells. These data demonstrate that geohelminth-associated Treg influence immune responses to bystander Ag of mycobacteria and plasmodia. Geohelminth-induced immune modulation may have important consequences for co-endemic infections and vaccine trials. [source] Phenotypic analysis of human peripheral blood regulatory T cells (CD4+FOXP3+CD127lo/,) ex vivo and after in vitro restimulation with malaria antigensEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2010Olivia C. Finney Abstract Regulatory T cells (Treg) play crucial roles in regulating autoimmune responses and immunity to tumors and infectious diseases. However, numerous subpopulations of Treg are now being described and the utility of various Treg markers is being reassessed. Here we report the results of a detailed phenotypic comparison of two supposedly regulatory human T-cell populations, namely CD4+FOXP3+ T cells and CD4+CD25hi T cells. We find that CD4+FOXP3+ cells are extremely heterogeneous with respect to CD25 expression and that FOXP3+ and CD25hi CD4+ T cells differ in their expression of chemokine receptors (CCR), CD95 and Bcl-2, suggestive of distinct migration characteristics and susceptibility to apoptosis. Further, we propose that CD25 expression should be regarded as an activation marker rather than as a defining marker of Treg. Lastly, CD4+FOXP3+ T cells activated in vitro with malaria antigen expressed the highest levels of CCR4 and CD95, and the lowest levels of CCR7, indicating that they are most likely generated from effector memory cells during an immune response and rapidly succumb to apoptosis at the end of the response. [source] Regulatory T cells for the prevention of graft- versus -host disease: Professionals defeat amateursEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2009Matthias Edinger Abstract CD4+CD25+ Treg are pivotal for the maintenance of self-tolerance and the adoptive transfer of Treg is envisaged for the treatment of autoimmune diseases and the induction of tolerance after allogeneic organ or stem cell transplantation. Owing to the paucity of natural Treg in peripheral blood, isolation of Treg for therapeutic purposes is cumbersome and not easily translatable into clinical trials. To circumvent such hurdles, many groups are exploring the de novo induction of Treg from conventional T cells for potential clinical applications. In this issue of the European Journal of Immunology, a paper examines the therapeutic efficacy of natural and induced Treg in a model of graft- versus -host disease and report that induced Treg rapidly lose their Treg features in an allogeneic environment and are unable to prevent disease. Thus, the stability of induced Treg is of major concern as discussed in this Commentary. [source] Regulatory T cells in the past and for the futureEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008Shimon Sakaguchi Dr. No Abtract [source] Regulatory T cells and immune computationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008Francisco J. Quintana Dr. Abstract The role of Treg in immune regulation is the topic of this Viewpoint series in the European Journal of Immunology (EJI); the question to be discussed in this section is the effector function of Treg in immune regulation. In this manuscript, we take on the following three postulates outlined by Rolf Zinkernagel on the role of Treg in the control of immunity. First, the immune response is regulated primarily by the antigen and not by Treg. Second, immune non-responsiveness results from the deletion of specific receptor-bearing T cells. Third, there is no definitive proof of the existence of specialized Treg that know what is needed for an equilibrated immune response. Herein, we discuss data demonstrating the existence of specialized Treg and therefore arguing against the validity of the first two postulates. However, based on the reactive nature of the immune system, we agree with Rolf's third postulate in that Treg cannot know ahead of time an ideal set-point for immune homeostasis. See accompanying commentary: http://dx.doi.org/10.1002/eji.200738114 [source] Naturally Occurring Regulatory T cells (CD4+, CD25high, FOXP3+) in the Antrum and Cardia are Associated with Higher H. pylori Colonization and Increased Gene Expression of TGF-,1HELICOBACTER, Issue 4 2008Arne Kandulski Abstract Background:Helicobacter pylori causes gastric inflammation. Despite the induction of H. pylori -specific B- and T cells, the immune response is not sufficient to clear the infection. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. FOXP3 was shown to be expressed in a subset of Treg cells known as ,naturally occurring Treg cells'. These cells have not been sufficiently studied in context to H. pylori -induced inflammation in human gastric mucosa. Materials and methods: The study included 76 patients stratified according to the presence of H. pylori. Gene expression levels of FOXP3, transforming growth factor (TGF)-,1, and interleukin-10 were analyzed by quantitative real-time polymerase chain reaction in biopsies from gastric antrum, corpus, and cardia. FOXP3 expression was also analyzed by immunohistochemistry. Differences in expression levels were analyzed by comprehensive statistical analyses and correlated with clinical and histomorphologic parameters. Results:H. pylori -positive patients revealed a 19- to 25-fold induction of FOXP3 transcript levels in antrum and cardia (p < .02). FOXP3 transcript levels correlated positively with inflammation (p < .04) and TGF-,1 transcript levels (p < .001). Furthermore, a positive correlation between FOXP3+ Treg cells and H. pylori colonization was demonstrated. Conclusion: This study demonstrates that H. pylori -induced gastritis is associated with a recruitment of naturally occurring FOXP3+ Treg cells that correlates with the degree of bacterial colonization and mucosal TGF-,1 expression. Together, these data support the hypothesis that naturally FOXP3+ Treg cells play a role in the lifelong persistence of H. pylori infection in humans. [source] Regulatory T cells and intestinal homeostasisIMMUNOLOGICAL REVIEWS, Issue 1 2005Janine L. Coombes Summary:, Murine models of inflammatory bowel disease (IBD) are useful tools for the study of the pathogenesis and regulation of intestinal inflammation. Colitis can be induced in immune-deficient mice following transfer of populations of T cells or following infection with Helicobacter hepaticus and other intestinal pathogens. In these situations, colitis occurs as a result of the absence of a specialized population of regulatory cells, as transfer of CD4+CD25+ T cells prevents disease. Importantly, from a clinical perspective, CD4+CD25+ T cells can also reverse an established colitis. CD4+CD25+ T cells proliferate both in the secondary lymphoid organs and at the site of inflammation, suggesting that regulation occurs both locally and systemically. CD4+CD25+ T cells are not only capable of regulating other T cells but are also capable of suppressing components of the innate immune system. Control of colitis is dependent on the presence of the immunosuppressive cytokines interleukin-10 and transforming growth factor-,, although their roles are divergent and complex. Regulatory T cells represent one of the host's mechanisms to prevent immune pathology during chronic immune stimulation. Enhancement of regulatory T-cell activity may be useful to control autoreactive T-cell responses and inhibit harmful inflammatory diseases such as asthma and IBD. [source] Regulatory T cells and autoimmune diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2005Silke Paust Summary:, Although T-cell clones bearing T-cell receptors with high affinity for self-peptide major histocompatibility complex (MHC) products are generally eliminated in the thymus (recessive tolerance), the peripheral T-cell repertoire remains strongly biased toward self-peptide MHC complexes and includes autoreactive T cells. A search for peripheral T cells that might exert dominant inhibitory effects on autoreactivity has implicated a subpopulation of CD4+CD25+ T cells called regulatory T cells (Tregs). Here, we discuss the role of cytokines and costimulatory molecules in the generation, maintenance, and function of Tregs. We also summarize evidence for the involvement of Tregs in controlling autoimmune diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and inflammatory bowel disease. Last, we discuss our recent definition of the potential role of B7 expressed on activated T-effector cells as a target molecule for Treg-dependent suppression. These observations suggest that the engagement of B7 on effector T cells transmits an inhibitory signal that blocks or attenuates effector T-cell function. We restrict our comments to the suppression mediated by cells within the CD4 lineage; the impact of the cells within the CD8 lineage that may suppress via engagement of Qa-1 on effector T cells is not addressed in this review. [source] Regulatory T cells and tumour immunity , observations in mice and menIMMUNOLOGY, Issue 2 2008Awen Gallimore Summary An enormous body of work supports a role for CD4+ CD25+ regulatory cells (Tregs) in shaping the immune response to tumours. Indeed, there is evidence that the cells impede effective tumour immunosurveillance, inhibit vaccine-induced antitumour immune responses and promote tumour progression. Studies exploring the impact of Tregs on tumour development are discussed in the context of manipulating this T-cell population for the purpose of cancer immunotherapy. [source] Regulatory T cells in human disease and their potential for therapeutic manipulationIMMUNOLOGY, Issue 1 2006Leonie S. Taams Summary Regulatory T cells are proposed to play a central role in the maintenance of immunological tolerance in the periphery, and studies in many animal models demonstrate their capacity to inhibit inflammatory pathologies in vivo. At a recent meeting [Clinical Application of Regulatory T Cells, 7,8 April 2005, Horsham, UK, organized by the authors of this review, in collaboration with the British Society for Immunology and Novartis] evidence was discussed that certain human autoimmune, infectious and allergic diseases are associated with impaired regulatory T-cell function. In contrast, evidence from several human cancer studies and some infections indicates that regulatory T cells may impair the development of protective immunity. Importantly, certain therapies, both those that act non-specifically to reduce inflammation and antigen-specific immunotherapies, may induce or enhance regulatory T-cell function. The purpose of this review was to summarize current knowledge on regulatory T-cell function in human disease, and to assess critically how this can be tailored to suit the therapeutic manipulation of immunity. [source] Session 02: Regulatory T cellsIMMUNOLOGY, Issue 2001Article first published online: 28 JUN 200 No abstract is available for this article. [source] Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neckJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1-2 2010Jan Boucek Abstract Regulatory T cells (Treg) are important regulators of anti-cancer immune responses, and an increase in Treg frequency was observed in the blood of cancer patients. Blood samples from 112 patients with head and neck squamous cell carcinoma antigen (HNSCC) were obtained at the time of tumour diagnosis, and lymphocyte subpopulations (CD3+; CD3,CD16+CD56+; CD4+; CD8+; CD19+; CD4+CD45RA+) with emphasis on Treg counts (CD3+CD4+CD25+), complete blood count and tumour markers (squamous cell carcinoma [SCC]; CEA; ,-1-antitrypsin [AAT]; Cyfra 21,1; C-reactive protein [CRP]) were analysed. The data were grouped according to TNM classification, and their significance for the course of the disease at an interval of 1 year after the end of the therapy was determined. The percentage of CD8+ cells increased and the CD/D8 ratio decreased with tumour grade. The ratio of B lymphocytes decreased in patients with locoregional metastases (11.25%versus 9.22%). Treg (15.2%) and CD4+ cells (45.3%) increased, while NK cells (11.8%) decreased in HNSCC patients compared to controls (9.0%, 38.1% and 15.8%, respectively). The data obtained at time of diagnosis were used to assess the significance of tumour markers (SCC, Cyfra 21,1 and AAT) for evaluation of prognosis. The erythrocyte counts (4.64 × 1012/l versus 4.45 × 1012/l) and haemoglobin levels (14.58 g/dl versus 14.05 g/dl) decreased, while Treg counts (8.91%versus 15.70%) increased in patients with early recurrence. Our results show that examination of these parameters could be helpful for prognostication in HNSCC patients and aid improvement of treatment strategy. [source] Regulatory T cell activity in primary and persistent Epstein,Barr virus infectionJOURNAL OF MEDICAL VIROLOGY, Issue 5 2009P.J. Wingate Abstract Regulatory T cells (Treg) provide a balance to immune T cell activation thereby protecting the body from pathogen-induced immunopathology. Several persistent viruses induce Treg that subvert protective immune mechanisms and promote viral persistence. Epstein,Barr virus (EBV) generally infects children subclinically and persists thereafter, but primary infection in early adulthood may cause immunopathological damage manifest as infectious mononucleosis. In this study the role of Treg was investigated in acute infectious mononucleosis and healthy EBV seropositive donors. The proportion of CD4+CD25high T cells in blood from infectious mononucleosis patients was significantly lower than in seropositive donors (P,=,0.05). Using the FOXP3 marker for Treg the same frequency and extra-follicular distribution of Treg was noted in infectious mononucleosis and control tonsils. Regulatory cytokines, interleukin (IL)-10 and transforming growth factor (TGF)-,, were significantly raised in infectious mononucleosis compared to seropositive donor plasma (P,=,0.0001, P,=,0.0004 respectively) although levels of IL-10 peaked earlier in infectious mononucleosis than TGF-,. Previous studies identified EBV latent membrane protein (LMP)-1-induced Treg activity [Marshall et al. (2003): J Immunol 170:6183,6189; Marshall et al. (2007): Brit J Haematol 139:81,89], and in this study a significant reduction in interferon-, production was found from infectious mononucleosis but not seropositive donor lymphocytes after stimulation with a recall antigen when LMP-1 peptide PRG was added (P,=,0.03). It is possible that Treg are important in controlling primary EBV infection to a subclinical level in most cases and that infectious mononucleosis represents a failure of this protective mechanism. J. Med. Virol. 81:870,877, 2009. © 2009 Wiley-Liss, Inc. [source] X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohortsALLERGY, Issue 7 2010R. W. B. Bottema To cite this article: Bottema RWB, Kerkhof M, Reijmerink NE, Koppelman GH, Thijs C, Stelma FF, Smit HA, Brunekreef B, van Schayck CP, Postma DS. X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts. Allergy 2010; 65: 865,874. Abstract Background:, The Forkhead Box P3 (FOXP3) gene, located on the X-chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single-nucleotide polymorphisms (SNPs) of FOXP3 are associated with atopy development in childhood. Methods:, Seven SNPs in FOXP3 were genotyped in 3062 children (51% boys) participating in the Allergenic study, which consists of three Dutch birth cohorts (PIAMA, PREVASC and KOALA). Association of FOXP3 SNPs with total serum IgE and sensitisation (presence of specific serum IgE to egg, milk, and indoor, i.e. house-dust mite, cat, and/or dog allergens) was investigated at ages 1, 2, 4, and 8. Analysis of variance and logistic regression were performed, stratified for gender. Results:, Our most consistent finding was observed for sensitisation to egg and indoor allergens. In girls, five FOXP3 SNPs (rs5906761, rs2294021, rs2294019, rs6609857 and rs3761548) were significantly associated with sensitisation to egg at ages 1 and 2 and with sensitisation to indoor allergens at age 2 (P < 0.05), but not at 4 and 8, a finding that was observed across the three cohorts. Rs5906761 and rs2294021 were associated with remission of sensitisation to food allergens in boys, as tested in the PIAMA cohort. Conclusion:, This is the first study showing across three cohorts that X-chromosomal FOXP3 genotypes may contribute to development of sensitisation against egg and indoor allergens in girls in early childhood. In addition, an association with remission of sensitisation to food allergens existed in boys only. [source] Low-dose cyclosporine A therapy increases the regulatory T cell population in patients with atopic dermatitisALLERGY, Issue 11 2009C. Brandt Background:, Atopic dermatitis (AD) is a T cell dependent chronic relapsing inflammatory skin disorder successfully treated with cyclosporine A (CsA). Clinical observations indicate that even low-dose CsA therapy is successful in severely affected AD patients. We studied the impact of low-dose CsA therapy on the ability of T helper cells to be activated, and examined whether regulatory T (Treg) cells are increased in these patients. Methods:, Peripheral T cells were activated in a whole blood sample and interleukin-2 producing cells were measured by intracellular cytokine staining. Regulatory T cells were analyzed by intracellular FoxP3 staining. Regulatory T cells (CD4+CD25+CD127low) and effector T cells (CD4+CD25,CD127+) were sorted by flow cytometry and used for suppression assays. Results:, A group of AD patients treated with low-dose CsA had a significantly larger Treg cell population than a healthy control subject group. In individual patients, onset of low-dose CsA therapy reduced the ability of T cells to be activated to 42 ± 18% (P < 0.005) and significantly increased Treg cells, both in absolute numbers (1.6-fold change) and frequencies (1.7-fold change). Treg cells from AD patients showed similar suppressive capacities as Treg cells from healthy donors. Furthermore, Treg cells from AD patients had skin homing properties. Conclusion:, Our results indicate that the therapeutic effect of low-dose CsA therapy in AD patients might be not only mediated by the inhibition of T cell hyperactivity but also by an increased population of Treg cells. [source] Regulatory T cells in bronchial asthmaALLERGY, Issue 3 2009K. Ryanna The main focus of this review was the role of a specific subset of T cells with immunomodulatory or immunosuppressive activities, termed regulatory T cells (Tregs), in the pathogenesis and treatment of bronchial asthma. Evidence that these cells are important in maintaining immune homeostasis in health and exhibit impaired activity in active disease will be discussed. Their therapeutic potential is perhaps best highlighted by evidence that therapies with demonstrated efficacy in allergic and asthmatic disease are associated with the induction or restoration of regulatory T-cell function, e.g. glucocorticoids, allergen immunotherapy. Strategies to improve the safety and efficacy of these treatments and that induce or boost Tregs in bronchial asthma are discussed. [source] | |||||||||||||||||||||||||||||||||||||