Search results for "anergy"
showing 10 items of 18 documents
Peroxisome proliferator-activated receptor alpha deficiency impairs regulatory T cell functions: Possible application in the inhibition of melanoma t…
2016
International audience; Regulatory T (Treg) cells are important to induce and maintain immunological self-tolerance. Although the progress accomplished in understanding the functional mechanism of Treg cells, intracellular molecules that control the mechanisms of their suppressive capacity are still on investigation. The present study showed that peroxisome proliferator-activated receptor-alpha deficiency impaired the suppressive activity of Treg cells on CD4(+)CD25(-) and CD8(+) T cell proliferation. In Treg cells, PPARα gene deletion also induced a decrease of migratory abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8 and CXCR-4) and p27(KIP1) mRNA. Treg ce…
Mycobacterial antigen(s) induce anergy by altering TCR- and TCR/CD28-induced signalling events: insights into T-cell unresponsiveness in leprosy.
2009
Present study investigates the role of Mycobacterium leprae (M. leprae) antigens on TCR- and TCR/CD28-induced signalling leading to T-cell activation and further correlates these early biochemical events with T-cell anergy, as prevailed in advanced stages of leprosy. We observed that both whole cell lystae (WCL) and soluble fraction of M. leprae sonicate (MLSA) not only inhibited TCR, thapsigargin and ionomycin induced calcium fluxes by diminishing the opening of calcium channels, but also TCR- or TCR/CD28-induced proximal signalling events like phosphorylation of Zap-70 and protein kinase-C (PKC) activity. Study of TCR- and TCR/CD28-induced downstream signals revealed that M. leprae antige…
The role of ICOS in directing T cell responses: ICOS-dependent induction of T cell anergy by tolerogenic dendritic cells.
2009
Abstract Tolerogenic dendritic cells (DC) play an important role in maintaining peripheral T cell tolerance in steady-state conditions through induction of anergic, IL-10-producing T cells with suppressive properties. ICOS, an activation-induced member of the CD28 family on T cells, is involved in the induction of IL-10, which itself could contribute to induction of anergy and development of suppressive T cells. Therefore, we analyzed the functional role of ICOS in the differentiation process of human CD4+ T cells upon their interaction with tolerogenic DC. We compared the functional properties of CD4+ T cells from healthy volunteers and ICOS-deficient patients after stimulation with tolero…
B cells participate in thymic negative selection of murine auto-reactive CD4+ T cells.
2010
It is well documented that thymic epithelial cells participate in the process of negative selection in the thymus. In recent years it was reported that also dendritic cells enter the thymus and contribute to this process, thus allowing for the depletion of thymocytes that are specific to peripherally expressed self-antigens. Here we report that also B cells may take part in the elimination of auto-reactive thymocytes. Using a unique mouse model we show that B cells induce negative selection of self-reactive thymocytes in a process that leads to the deletion of these cells whereas regulatory T cells are spared. These findings have direct implication in autoimmunity, as expression of a myelin…
CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity.
2002
Interleukin-10 (IL-10)–treated dendritic cells (DCs) induce an alloantigen- or peptide-specific anergy in various CD4+ and CD8+ T-cell populations. In the present study, we analyzed whether these anergic T cells are able to regulate antigen-specific immunity. Coculture experiments revealed that alloantigen-specific anergic CD4+ and CD8+ T cells suppressed proliferation of syngeneic T cells in a dose-dependent manner. The same effect was observed when the hemagglutinin-specific CD4+T-cell clone HA1.7 or tyrosinase-specific CD8+ T cells were cocultured with anergic T cells of the same specificity. Anergic T cells did not induce an antigen-independent bystander inhibition. Suppression was depe…
Sequestration of T lymphocytes to body fluids in tuberculosis: reversal of anergy following chemotherapy.
1999
The specificity of CD4 T lymphocytes was investigated in 6 patients affected by tuberculosis who had negative tuberculin purified protein derivative (PPD) skin tests at diagnosis. Polyclonal CD4 T cell lines from the peripheral blood failed to proliferate to PPD and to the 16- or 38-kDa proteins of Mycobacterium tuberculosis, while CD4 cell lines from the disease site responded to PPD and to the 16- and 38-kDa proteins and derived epitopes in vitro. Four months after chemotherapy, the patients became responsive to PPD. The proliferative response to PPD and to the 16- or 38-kDa proteins and their derived peptides decreased in CD4 T cell lines from the disease site and increased in lines from…
MAP kinase p38 and its relation to T cell anergy and suppressor function of regulatory T cells
2008
Diverse regulatory T cell populations (Treg) are important for the control of self tolerance and immune homeostasis. These include naturally occurring CD4+CD25+ Treg (nTreg) and induced Treg (iTreg). Tolerogenic dendritic cells, modulated by IL-10, are able to convert peripheral T cells into iTreg. These are anergic and characterized by a G(1) cell cycle arrest, dependent on elevated levels of the cdk inhibitor p27(Kip1). Novel data revealed a distinct pattern of MAP kinase activation in iTreg different from clonal T cell anergy, with enhanced activation of the p38-MAPKAP-K2/3 pathway. p38 is involved in cell cycle control and its activity is a prerequisite for the induction and maintenance…
NFAT transcription factors in control of peripheral T cell tolerance.
2006
The Ca++-regulated calcineurin/NFAT cascade is one of the crucial signalling pathways that controls adaptive immunity. However, a number of novel experimental data suggest that, in addition to their role in T cell activation, NFATc transcription factors play also a decisive role in the generation of peripheral tolerance against self-antigens. This function of NFATc factors is mediated by controlling activation-induced cell death and clonal anergy of T helper cells and the activity of regulatory T cells. The multi-functional role of NFATc proteins characterize these transcription factors as key regulators of immunological tolerance and, if dysregulated, of development of autoimmune diseases.
The Role of Interleukin 10 in the Regulation of Allergic Immune Responses
2001
Several clinical studies and animal models have shown that Th2 lymphocytes play a key role in the pathophysiology of IgE-mediated allergic immune responses like allergic rhinitis and asthma or venom anaphylaxis. Classical specific immunotherapy (SIT) that has been proven to be clinically effective can serve as a role model for immunological changes that are associated with amelioration of allergic diseases. During SIT, the Th2-dominated immune response is modified towards a Th1 response leading to a decline in allergen-specific IgE and an increase in allergen-specific IgG production. Most importantly, however, production of the immunosuppressive/-regulatory cytokine interleukin 10 (IL-10) i…
Interferon-α Abrogates Tolerance Induction by Human Tolerogenic Dendritic Cells
2011
Background Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs). Methodology/Principal Findings IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an…