CD28 Costimulation: From Mechanism to Therapy.
CD28 Costimulation: From Mechanism to Therapy.
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DOI：
10.1016/j.immuni.2016.04.020
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发表时间：
2016-05-17
期刊：
影响因子：
32.4
通讯作者：
Bluestone JA
中科院分区：
文献类型：
--
作者：
Esensten JH;Helou YA;Chopra G;Weiss A;Bluestone JA
T细胞上的CD 28受体的连接与T细胞受体（TCR）连接一起为初始T细胞活化提供了关键的第二信号。在这里，我们讨论的表达，结构和生物化学的CD 28及其配体。CD 28信号在许多T细胞过程中起关键作用，包括细胞骨架重塑、细胞因子的产生、存活和分化。CD 28连接导致T细胞中独特的表观遗传、转录和翻译后变化，这些变化不能通过单独的TCR连接重现。我们讨论了CD 28及其配体在效应T细胞和调节T细胞中的功能。CD 28对于调节性T细胞存活和维持免疫稳态至关重要。我们概述了CD 28及其家族成员在人类疾病中的作用，并回顾了阻断CD 28配体的药物的临床疗效。尽管CD 28及其家族成员和配体对免疫功能具有中心作用，但CD 28生物学的许多方面仍不清楚。将对CD 28功能的基本理解转化为免疫调节疗法是不平衡的，既有成功也有失败。这种真实世界的结果可能源于多种因素，包括CD 28家族成员之间复杂的受体-配体相互作用、小鼠和人CD 28家族之间的差异以及CD 28家族成员的细胞类型特异性作用。
Ligation of the CD28 receptor on T cells provides a critical second signal alongside T cell receptor (TCR) ligation for naive T cell activation. Here we discuss the expression, structure, and biochemistry of CD28 and its ligands. CD28 signals play a key role in many T cell processes including cytoskeletal remodeling, production of cytokines, survival, and differentiation. CD28 ligation leads to unique epigenetic, transcriptional, and post-translational changes in T cells that cannot be recapitulated by TCR ligation alone. We discuss the function of CD28 and its ligands in both effector and regulatory T cells. CD28 is critical for regulatory T cell survival and the maintenance of immune homeostasis. We outline the roles that CD28 and its family members play in human disease and we review the clinical efficacy of drugs that block CD28 ligands. Despite the centrality of CD28 and its family members and ligands to immune function, many aspects of CD28 biology remain unclear. Translation of a basic understanding of CD28 function into immunomodulatory therapeutics has been uneven with both successes and failures. Such real-world results may stem from multiple factors including complex receptor-ligand interactions among CD28 family members, differences between the mouse and human CD28 families, and cell-type specific roles of CD28 family members.