1,721,008 research outputs found
Glimpsing the real CD4+ T cell response
No full textThe present views of how CD4(+) T cells respond to antigen are based largely on artificial systems. A highly sensitive approach that allows normal T cell responses to be monitored in physiological conditions overturns some existing ideas about the differentiation of CD4(+) T cells.X1122sciescopu
IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis
No full textAfter their development in the thymus, mature T cells are maintained in the periphery by two sets of survival signals, namely TCR signals from contact with self-peptide/MHC ligands and the cytokine receptor signals from binding IL-7 and IL-15. These signals cooperate to maximize the utility of finite resources to support a diverse pool of mature T cells. It is becoming increasingly clear that multiple mechanisms exist to regulate expression of IL-7R at the transcriptional and post-translational levels. The interplay between TCR signals and IL-7R signals are also important in regulation of IL-7R expression. This review will focus on regulation of T cell homeostasis by IL-7R signaling, with an emphasis on the cross talk between signals from TCR and IL-7R. (C) 2012 Elsevier Ltd. All rights reserved.X1180sciescopu
TGF-Beta puts the brakes on homeostatic proliferation
No full textThe cellular mechanism by which the cytokine TGF-beta maintains the homeostasis of mature T cells and prevents the emergence of severe lethal lymphoproliferative disease has remained obscure. It is now shown that TGF-b restrains the homeostatic T cell proliferation driven by self ligands from erupting into overt autoimmunity.X1187sciescopu
In vivo accumulation of T cells in response to IL-2/anti-IL-2 mAb complexes is dependent in part on the TNF family ligand 4-1BBL
No full textImmune complexes combining IL-2 with particular anti-IL-2 antibodies can be used to selectively expand regulatory T cells or memory T cells. Combining IL-2 with anti-IL-2 (Clone S4B6) greatly enhances the biological potency of IL-2 in vivo leading to selective expansion of CD8 memory T cells and NK cells compared with regulatory T cells. Here we show that in vivo administration of IL-2/anti-IL-2 mAb (IL-2/mAb) complexes induces 4-1BB expression on both adoptively transferred antigenspecific memory CD8 T cells as well as on endogenous memory phenotype cells. Remarkably, the accumulation of adoptively transferred memory CD8 T cells following in vivo IL-2/mAb-complex treatment was found to be dependent in part on the presence of 4-1BBL in the host. These effects were independent of IL-2-induced cell division, suggesting that 4-1BBL-induced survival signals contribute to IL-2/mAb-complex-induced T-cell accumulation in vivo. Immunology and Cell Biology (2012) 90, 743-747; doi:10.1038/icb.2011.83; published online 27 September 2011X1145sciescopu
T Cell Receptor-Dependent Regulation of Lipid Rafts Controls Naive CD8(+) T Cell Homeostasis
No full textT cell receptor (TCR) contact with self ligands keeps T cells alive and is shown here to cause naive CD8(+), but not CD4(+), T cells to be hypersensitive to certain gamma(c) cytokines, notably interleukin (IL)-2, IL-15, and IL-7. Hypersensitivity of CD8(+) T cells to IL-2 was dependent on a low-level TCR signal, associated with high expression of CD5 and GM1, a marker for lipid rafts, and was abolished by disruption of lipid rafts. By contrast, CD4(+) T cells expressed low amounts of GM1 and were unresponsive to IL-2. Physiologically, sensitivity to IL-7 and IL-15 maintains survival of resting CD8(+) T cells, whereas sensitivity to IL-2 may be irrelevant for normal homeostasis but crucial for the immune response. Thus, TCR contact with antigen upregulates GM1 and amplifies responsiveness of naive CD8(+) T cells to IL-2, thereby making the cells highly sensitive to exogenous IL-2 from CD4(+) T helper cells.X117575sciescopu
Is IL-7 from dendritic cells essential for the homeostasis of CD4(+) T cells?
No full textX1177sciescopu
Blowing on embers: commensal microbiota and our immune system
Full text linkVertebrates have co-evolved with microorganisms resulting in a symbiotic relationship, which plays an important role in health and disease. Skin and mucosal surfaces are colonized with a diverse population of commensal microbiota, over 1000 species, outnumbering the host cells by 10-fold. In the past 40 years, studies have built on the idea that commensal microbiota is in constant contact with the host immune system and thus influence immune function. Recent studies, focusing on mutualism in the gut, have shown that commensal microbiota seems to play a critical role in the development and homeostasis of the host immune system. In particular, the gut microbiota appears to direct the organization and maturation of lymphoid tissues and acts both locally and systemically to regulate the recruitment, differentiation, and function of innate and adaptive immune cells. While the pace of research in the area of the mucosal immune interface has certainly intensified over the last 10 years, we are still in the early days of this field. Illuminating the mechanisms of how gut microbes shape host immunity will enhance our understanding of the causes of immune-mediated pathologies and improve the design of next-generation vaccines. This review discusses the recent advances in this field, focusing on the close relationship between the adaptive immune system and commensal microbiota, a constant and abundant source of foreign antigens.open112934sciescopu
Unique Features of Naive CD8+ T Cell Activation by IL-2
No full textIL-2 has a pervasive influence on the immune system and dictates the survival and differentiation of multiple T cell subsets, including CD4 regulatory T cells, CD4 Th cells, and CD8 memory cells. IL-2 is synthesized by T cells during the early stages of the immune response and promotes T cell expansion and effector cell generation after initial activation via TCR signaling. Based on studies with activated T cell lines maintained in vitro, IL-2 is known to activate multiple signaling pathways that show considerable overlap with the pathways elicited via the TCR. In this paper, we have examined IL-2 signaling under TCR-independent conditions, namely by culturing purified resting naive CD8 T cells with IL-2 in the absence of Ag or APC. Under these conditions, we show in this study that IL-2 elicits a unique pattern of signaling associated with strong lymphocyte-specific protein tyrosine kinase/JAK3-dependent activation of the PI3K/AKT pathway with little or no involvement of STAT5, NF-kappa B, or the calcineurin/NFAT pathways. Such signaling induces marked proliferation associated with rapid and selective expression of eomesodermin but not T-bet and differentiation into long-lived central memory cells after adoptive transfer.X1117sciescopu
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