Esensten Jonathan H, Helou Ynes A, Chopra Gaurav, Weiss Arthur, Bluestone Jeffrey A
Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
Division of Rheumatology, Department of Medicine, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA 94143, USA.
Immunity. 2016 May 17;44(5):973-88. doi: 10.1016/j.immuni.2016.04.020.
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 might 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.
T细胞上CD28受体的结合与T细胞受体（TCR）结合一起，为初始T细胞激活提供关键的第二信号。在此，我们讨论CD28及其配体的表达、结构和生物化学。CD28信号在许多T细胞过程中发挥关键作用，包括细胞骨架重塑、细胞因子产生、存活和分化。CD28结合导致T细胞中独特的表观遗传、转录和翻译后变化，这些变化无法仅通过TCR结合来重现。我们讨论CD28及其配体在效应T细胞和调节性T细胞中的功能。CD28对调节性T细胞存活和免疫稳态的维持至关重要。我们概述了CD28及其家族成员在人类疾病中的作用，并综述了阻断CD28配体的药物的临床疗效。尽管CD28及其家族成员和配体在免疫功能中处于核心地位，但CD28生物学的许多方面仍不清楚。将对CD28功能的基本理解转化为免疫调节疗法的过程并不顺利，有成功也有失败。这种实际结果可能源于多种因素，包括CD28家族成员之间复杂的受体-配体相互作用、小鼠和人类CD28家族之间的差异以及CD28家族成员的细胞类型特异性作用。
