共查询到20条相似文献,搜索用时 15 毫秒
1.
Mucida D Park Y Kim G Turovskaya O Scott I Kronenberg M Cheroutre H 《Science (New York, N.Y.)》2007,317(5835):256-260
The cytokine transforming growth factor-beta (TGF-beta) converts na?ve T cells into regulatory T (Treg) cells that prevent autoimmunity. However, in the presence of interleukin-6 (IL-6), TGF-beta has also been found to promote the differentiation of na?ve T lymphocytes into proinflammatory IL-17 cytokine-producing T helper 17 (T(H)17) cells, which promote autoimmunity and inflammation. This raises the question of how TGF-beta can generate such distinct outcomes. We identified the vitamin A metabolite retinoic acid as a key regulator of TGF-beta-dependent immune responses, capable of inhibiting the IL-6-driven induction of proinflammatory T(H)17 cells and promoting anti-inflammatory Treg cell differentiation. These findings indicate that a common metabolite can regulate the balance between pro- and anti-inflammatory immunity. 相似文献
2.
3.
4.
Li B Yu H Zheng W Voll R Na S Roberts AW Williams DA Davis RJ Ghosh S Flavell RA 《Science (New York, N.Y.)》2000,288(5474):2219-2222
T helper 1 (TH1) cells mediate cellular immunity, whereas TH2 cells potentiate antiparasite and humoral immunity. We used a complementary DNA subtraction method, representational display analysis, to show that the small guanosine triphosphatase Rac2 is expressed selectively in murine TH1 cells. Rac induces the interferon-gamma (IFN-gamma) promoter through cooperative activation of the nuclear factor kappa B and p38 mitogen-activated protein kinase pathways. Tetracycline-regulated transgenic mice expressing constitutively active Rac2 in T cells exhibited enhanced IFN-gamma production. Dominant-negative Rac inhibited IFN-gamma production in murine T cells. Moreover, T cells from Rac2-/- mice showed decreased IFN-gamma production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression. 相似文献
5.
Rissoan MC Soumelis V Kadowaki N Grouard G Briere F de Waal Malefyt R Liu YJ 《Science (New York, N.Y.)》1999,283(5405):1183-1186
It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (TH1) or TH2 cells. Human monocyte (pDC1)-derived dendritic cells (DC1) were found to induce TH1 differentiation, whereas dendritic cells (DC2) derived from CD4+CD3-CD11c- plasmacytoid cells (pDC2) induced TH2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The TH2 cytokine IL-4 enhanced DC1 maturation and killed pDC2, an effect potentiated by IL-10 but blocked by CD40 ligand and interferon-gamma. Thus, a negative feedback loop from the mature T helper cells may selectively inhibit prolonged TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset. 相似文献
6.
Rubtsov YP Niec RE Josefowicz S Li L Darce J Mathis D Benoist C Rudensky AY 《Science (New York, N.Y.)》2010,329(5999):1667-1671
Tissue maintenance and homeostasis can be achieved through the replacement of dying cells by differentiating precursors or self-renewal of terminally differentiated cells or relies heavily on cellular longevity in poorly regenerating tissues. Regulatory T cells (T(reg) cells) represent an actively dividing cell population with critical function in suppression of lethal immune-mediated inflammation. The plasticity of T(reg) cells has been actively debated because it could factor importantly in protective immunity or autoimmunity. By using inducible labeling and tracking of T(reg) cell fate in vivo, or transfers of highly purified T(reg) cells, we have demonstrated notable stability of this cell population under physiologic and inflammatory conditions. Our results suggest that self-renewal of mature T(reg) cells serves as a major mechanism of maintenance of the T(reg) cell lineage in adult mice. 相似文献
7.
Much progress has been made in understanding how the immune system is regulated, with a great deal of recent interest in naturally occurring CD4+ regulatory T cells that actively engage in the maintenance of immunological self-tolerance and immune homeostasis. The challenge ahead for immunologists is the further elucidation of the molecular and cellular processes that govern the development and function of these cells. From this, exciting possibilities are emerging for the manipulation of regulatory T cell pathways in treating immunological diseases and suppressing or augmenting physiological immune responses. 相似文献
8.
Tuning of natural killer cell reactivity by NKp46 and Helios calibrates T cell responses 总被引:1,自引:0,他引:1
Narni-Mancinelli E Jaeger BN Bernat C Fenis A Kung S De Gassart A Mahmood S Gut M Heath SC Estellé J Bertosio E Vely F Gastinel LN Beutler B Malissen B Malissen M Gut IG Vivier E Ugolini S 《Science (New York, N.Y.)》2012,335(6066):344-348
9.
CTLA-4 control over Foxp3+ regulatory T cell function 总被引:1,自引:0,他引:1
Wing K Onishi Y Prieto-Martin P Yamaguchi T Miyara M Fehervari Z Nomura T Sakaguchi S 《Science (New York, N.Y.)》2008,322(5899):271-275
Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells. 相似文献
10.
The T cell receptor 总被引:51,自引:0,他引:51
The primary structure of T cell receptor proteins and genes is well understood. Immunologists are now trying to understand the properties of these interesting molecules. Evidence suggests that T cell alpha beta receptors recognize a complex of an antigen-derived peptide bound to one of the cell-surface products of the major histocompatibility complex (MHC) genes. It is likely that alpha beta receptors and MHC proteins have coevolved to have some affinity for each other. During T cell development in the thymus, cells bearing self-reactive receptors are deleted by the mechanisms of tolerance, and cells are preferentially allowed to mature if they bear receptors that will be able to recognize antigen plus self-MHC after they have become full-fledged T cells. Some explanations for these phenomena have been tested, but no satisfactory theory can yet be proposed to account for them. 相似文献
11.
Peng G Guo Z Kiniwa Y Voo KS Peng W Fu T Wang DY Li Y Wang HY Wang RF 《Science (New York, N.Y.)》2005,309(5739):1380-1384
CD4+ regulatory T (Treg) cells have a profound ability to suppress host immune responses, yet little is understood about how these cells are regulated. We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function. This effect was independent of dendritic cells but required functional TLR8-MyD88-IRAK4 signaling in Treg cells. Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity. These results suggest that TLR8 signaling could play a critical role in controlling immune responses to cancer and other diseases. 相似文献
12.
13.
14.
Human T cell antigen expression by primate T cells 总被引:16,自引:0,他引:16
B F Haynes D L Dowell L L Hensley I Gore R S Metzgar 《Science (New York, N.Y.)》1982,215(4530):298-300
15.
T cell activation by lipopeptide antigens 总被引:2,自引:0,他引:2
Moody DB Young DC Cheng TY Rosat JP Roura-Mir C O'Connor PB Zajonc DM Walz A Miller MJ Levery SB Wilson IA Costello CE Brenner MB 《Science (New York, N.Y.)》2004,303(5657):527-531
Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity. 相似文献
16.
Madakamutil LT Christen U Lena CJ Wang-Zhu Y Attinger A Sundarrajan M Ellmeier W von Herrath MG Jensen P Littman DR Cheroutre H 《Science (New York, N.Y.)》2004,304(5670):590-593
Memory T cells are long-lived antigen-experienced T cells that are generally accepted to be direct descendants of proliferating primary effector cells. However, the factors that permit selective survival of these T cells are not well established. We show that homodimeric alpha chains of the CD8 molecule (CD8alphaalpha) are transiently induced on a selected subset of CD8alphabeta+ T cells upon antigenic stimulation. These CD8alphaalpha molecules promote the survival and differentiation of activated lymphocytes into memory CD8 T cells. Thus, memory precursors can be identified among primary effector cells and are selected for survival and differentiation by CD8alphaalpha. 相似文献
17.
【目的】探讨Rho分子信号通路阻断剂盐酸法舒地尔(HA1077)对C3H10T1/2细胞体外增殖及成脂分化的影响。【方法】体外培养C3H10T1/2细胞株,用HA1077浓度梯度培养液(0(对照组),20,40,60,80,100μmol/L)对其进行处理,通过MTT比色法和油红O染色法分别检测C3H10T1/2细胞的增殖和分化情况。【结果】HA1077对C3H10T1/2细胞的体外增殖有一定的抑制作用,且呈现出一定的浓度依赖性。但HA1077可提高C3H10T1/2细胞的成脂分化效率,也呈浓度依赖性;且当HA1077浓度大于60μmol/L后,细胞成脂分化率与对照组差异极显著(P<0.01)。【结论】HA1077可抑制C3H10T1/2细胞的增殖,但同时可以促进其成脂分化。 相似文献
18.
Suppression of immune responses by regulatory T cells (Tregs) is thought to limit late stages of pathogen-specific immunity as a means of minimizing associated tissue damage. We examined a role for Tregs during mucosal herpes simplex virus infection in mice, and observed an accelerated fatal infection with increased viral loads in the mucosa and central nervous system after ablation of Tregs. Although augmented interferon production was detected in the draining lymph nodes (dLNs) in Treg-deprived mice, it was profoundly reduced at the infection site. This was associated with a delay in the arrival of natural killer cells, dendritic cells, and T cells to the site of infection and a sharp increase in proinflammatory chemokine levels in the dLNs. Our results suggest that Tregs facilitate early protective responses to local viral infection by allowing a timely entry of immune cells into infected tissue. 相似文献
19.
20.
Despite much progress in understanding how extrinsic signaling regulates stem cell self-renewal, little is known about how cell-autonomous gene regulation controls this process. In Drosophila ovaries, germline stem cells (GSCs) divide asymmetrically to produce daughter GSCs and cystoblasts, the latter of which develop into germline cysts. Here, we show that removing the translational repressor Nanos from either GSCs or their precursors, the primordial germ cells (PGCs), causes both cell types to differentiate into germline cysts. Thus, Nanos is essential for both establishing and maintaining GSCs by preventing their precocious entry into oogenesis. These functions are likely achieved by repressing the translation of differentiation factors in PGCs and GSCs. 相似文献