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Suppressive Properties (suppressive + property)
Selected AbstractsSuppressive properties of human CD4+CD25+ regulatory T,cells are dependent on CTLA-4 expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Brigitte Birebent Abstract It has been demonstrated that T,cells with regulatory properties are present within the peripheral blood CD4+CD25+ T,cell compartment. Here, we describe an original method to purify human CD4+CD25+CD152+ T,lymphocytes as living cells by forcing the exportation of CTLA-4 molecules stored in intracellular vesicules at the cell surface. By doing so, we demonstrate that CD4+CD25+ T,cells contain a smaller and more homogeneous population enriched in cells with in vitro regulatory activity. Moreover, we show that this enrichment in regulatory T,cells is associated with an increased expression of Foxp3 and that CD4+CD25+CD152+ T,lymphocytes display a much stronger suppressive activity in controlling in vitro proliferation of alloantigen-specific T,cells than CD4+CD25+CD152, T,lymphocytes purified in parallel. Lastly, by purifying such cells expressing CTLA-4, we demonstrate that indeed CTLA-4 is involved in CD4+CD25+CD152+ T,cell regulatory activity, while suppressive cytokines are not. [source] Interleukin-10-secreting T cells define a suppressive subset within the HIV-1-specific T-cell populationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2009Eirik A. Torheim Abstract Recent studies have indicated that Treg contribute to the HIV type 1 (HIV-1)-related immune pathogenesis. However, it is not clear whether T cells with suppressive properties reside within the HIV-1-specific T-cell population. Here, PBMC from HIV-1-infected individuals were stimulated with a 15-mer Gag peptide pool, and HIV-1-specific T cells were enriched by virtue of their secretion of IL-10 or IFN-, using immunomagnetic cell-sorting. Neither the IL-10-secreting cells nor the IFN-,-secreting cells expressed the Treg marker FOXP3, yet the IL-10-secreting cells potently suppressed anti-CD3/CD28-induced CD4+ as well as CD8+ T-cell proliferative responses. As shown by intracellular cytokine staining, IL-10- and IFN-,-producing T cells represent distinct subsets of the HIV-1-specific T cells. Our data collectively suggest that functionally defined HIV-1-specific T-cell subsets harbor potent immunoregulatory properties that may contribute to HIV-1-associated T-cell dysfunction. [source] Freeze-and-thaw-disrupted tumour cells impair the responsiveness of DC to TLR stimulationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2008Iņigo Tirapu Abstract Cancer immunotherapy aims at inducing immune responses against tumour-associated antigens that mediate the eradication of tumour cells. For successful vaccination against antigens expressed by the tumour, the immune system has to be provided with sufficient amounts of these antigens in connection with strong immunostimulatory signals such as toll-like receptor (TLR) ligands. Tumour cells represent a convenient source of relevant tumour-associated antigens but can have suppressive properties. In this study, we explored how different forms of tumour cell material influence the activation of dendritic cells (DC), which play a crucial role in the induction of anti-tumour immune responses. We show that freeze-and-thaw-disrupted tumour cells inhibit DC activation in response to TLR stimulation, a phenomenon that is only partially seen with non-disrupted control cells. This suppression of DC stimulation is independent of tumour cell- and species-specific factors. We tested the hypothesis that phosphatidylserine on cells with disrupted membrane integrity mediates inhibition of TLR-induced DC activation. Our experimental evidence indicates that phosphatidylserine is not involved in the inhibition of TLR-mediated DC activation by freeze-and-thaw-disrupted cells. The inhibitory activity associated with disrupted tumour cells could explain why such preparations are less effective tumour vaccines than apoptotic tumour cells. [source] Activated CD1d-restricted natural killer T cells secrete IL-2: innate help for CD4+CD25+ regulatory T cells?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2005Shuiping Jiang Abstract CD4+CD25+ and CD1d-restricted natural killer T (NKT) cells are thymus-derived self-reactive regulatory T,cells that play a key role in the control of pathological immune responses. Little is known about functional cooperation between innate regulatory NKT,cells and adaptive CD4+CD25+ regulatory cells. Here we show that human CD4+V,24+V,11+ (CD4+ NKT) cells isolated from peripheral blood by flow cytometric cell sorting secrete substantial amounts of IL-2 after stimulation with dendritic cells (DC) and ,-Galactosylceramide. When cocultured with CD4+CD25+ cells, CD4+ NKT,cells promoted moderate proliferation of CD4+CD25+ cells. The proliferation of CD4+CD25+ T,cells was due to soluble IL-2 produced by activated CD4+ NKT,cells. The expanded CD4+CD25+ cells remained anergic and retained their potent suppressive properties. These findings indicate that unlike conventional CD4+ and CD8+ T,cells, which are susceptible to CD4+CD25+ regulatory cell suppression, NKT,cells promote CD4+CD25+ regulatory cell proliferation. These data raise the possibility that NKT,cells can function as helper cells to CD4+CD25+ regulatory T,cells, thereby providing a link between the two naturally occurring populations of regulatory T,cells. [source] Aging-dependent generation of suppressive CD4+CD25,R123loCD103+ T,cells in miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2003Jun Shimizu Abstract Advancing age is associated with significant alterations in immune functions, including a decline in CD4 T,cell function, in both mice and humans. In our previous report, we showed that CD4+CD25, T,cells in aged (24-month-old) mice, especially after in vitro pre-stimulation of these cells, exhibit hyporesponsive and suppressive properties. We examined here whether the suppressive activity of aged CD4+CD25, T,cells is ascribable to a particular population within these cells. In vitro analyses revealed that cell populations rapidly extruding Rhodamine-123 (R123) (referred to as R123lo cells) in aged CD4+CD25, T,cells have a more potent suppressive function compared with R123hi populations. In addition, CD103+ cells in freshly prepared aged CD4+CD25,R123lo T,cells had a most potent suppressive activity. Both R123hi and R123lo populations had individually stronger suppressive activity after pre-stimulation than before pre-stimulation. Furthermore, the R123lo population in young CD4+CD25, T,cells also had different properties from R123hi T cells: low responsiveness, no additive effect in proliferation assays, and the gain of a suppressive function after in vitro pre-stimulation. Takentogether, these results suggest that CD4+CD25,R123lo T,cells are a unique population within whole CD4+CD25, T,cells. This population exists in the earlystage of the life span, and the properties in this population become obvious with aging, that is the gain of their suppressive activity. [source] Induction and mechanism of action of transforming growth factor-,-secreting Th3 regulatory cellsIMMUNOLOGICAL REVIEWS, Issue 1 2001Howard L. Weiner Summary: Th3 CD4+ regulatory cells were identified during the course of investigating mechanisms associated with oral tolerance. Different mechanisms of tolerance are induced following oral antigen administration, including active suppression, clonal anergy and deletion. Low doses favor active suppression whereas high doses favor anergy/deletion. Th3 regulatory cells form a unique T-cell subset which primarily secretes transforming growth factor (TGF)-,, provides help for IgA and has suppressive properties for both Th1 and Th2 cells. Th3 type cells are distinct from the Th2 cells, as CD4+ TGF-,-secreting cells with suppressive properties have been generated from interleukin (IL)-4-deficient animals. In vitro differentiation of Th3 cells from Th precursors from T-cell antigen receptor (TCR) transgenic mice is enhanced by culture with TGF-,, IL-4, IL-10, and anti-IL-12. Th3 CD4+ myelin basic protein regulatory clones are structurally identical to Th1 encephalitogenic clones in TCR usage, MHC restriction and epitope recognition, but produce TGF-, with various amounts of IL-4 and IL-10. Because Th3 regulatory cells are triggered in an antigen-specific fashion but suppress in an antigen-non-specific fashion, they mediate "bystander suppression" when they encounter the fed autoantigen at the target organ. In vivo induction of Th3 cells and low dose oral tolerance is enhanced by oral administration of IL-4. Anti-CD86 but not anti-CD80 blocks the induction of Th3 cells associated with low dose oral tolerance. Th3 regulatory cells have been described in other systems (e.g. recovery from experimental allergic encephalomyelitis) but may be preferentially generated following oral antigen administration due to the gut immunologic milieu that is rich in TGF-, and has a unique class of dendritic cells. CD4+CD25+ regulatory T-cell function also appears related to TGF-,. [source] Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term resultsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007M. LAZZERINI Summary Background Anti-tumour necrosis factor- , antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor- , suppressive properties. Aim To investigate the long-term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease. Methods Twenty-eight patients with refractory moderate-severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5,2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission. Results Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28). Conclusions Thalidomide seems to be effective in inducing long-term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose-dependent, thus allowing long-term remission before drug suspension. [source] | ||||||||||