CD28 and CTLA-4 coreceptor expression and signal transduction.
CD28 and CTLA-4 coreceptor expression and signal transduction.
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DOI：
10.1111/j.1600-065x.2009.00770.x
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发表时间：
2009-05
影响因子：
8.7
通讯作者：
Schneider H
中科院分区：
文献类型：
--
作者：
Rudd CE;Taylor A;Schneider H
T细胞的活化是由T细胞受体ζ/CD3和CD4-CD8-p56lck复合体的抗原特异性信号和辅助受体如CD28、可诱导共刺激分子、细胞毒性T淋巴细胞抗原-4、程序性死亡等提供的辅助信号共同介导的。CD28和ICOS提供促进和维持T细胞反应的积极信号，而CTLA-4和PD-1限制反应。刺激性和抑制性共信号之间的平衡决定了T细胞反应的终极本质，在这种反应中，对外来病原体的反应是在没有过度炎症和自身免疫的情况下实现的。在这篇综述中，我们概述了CD28和CTLA-4信号机制[涉及磷脂酰肌醇3激酶(PI3K)、生长因子受体结合蛋白2(GRB2)、细丝蛋白A、蛋白激酶Cθ(PKCθ)和磷酸酶]控制T细胞免疫的最新知识。我们还介绍了T细胞受体相互作用分子(TRIM)调节CTLA-4表面表达的最新发现，以及涉及CTLA-4激活PI3K和蛋白激酶B(PKB)/AKT的信号通路，通过该通路确保细胞在无能诱导条件下存活。
T-cell activation is mediated by antigen-specific signals from the TCRζ/CD3 and CD4–CD8–p56lck complexes in combination with additional co-signals provided by coreceptors such as CD28, inducible costimulator (ICOS), cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death (PD-1), and others. CD28 and ICOS provide positive signals that promote and sustain T-cell responses, while CTLA-4 and PD-1 limit responses. The balance between stimulatory and inhibitory co-signals determines the ultimate nature of T-cell responses where response to foreign pathogen is achieved without excess inflammation and autoimmunity. In this review, we outline the current knowledge of the CD28 and CTLA-4 signaling mechanisms [involving phosphatidylinositol 3 kinase (PI3K), growth factor receptor-bound protein 2 (Grb2), Filamin A, protein kinase C θ (PKCθ), and phosphatases] that control T-cell immunity. We also present recent findings on T-cell receptor-interacting molecule (TRIM) regulation of CTLA-4 surface expression, and a signaling pathway involving CTLA-4 activation of PI3K and protein kinase B (PKB)/AKT by which cell survival is ensured under conditions of anergy induction.