Mondino A, Jenkins M K
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455.
J Leukoc Biol. 1994 Jun;55(6):805-15. doi: 10.1002/jlb.55.6.805.
The activation and eventual clonal expansion of individual antigen-specific CD4+ T cell clones are dependent on the production of autocrine growth factors such as interleukin-2 (IL-2). The specificity of CD4+ T cell activation is imparted by T cell antigen receptor (TCR) recognition of peptide antigens bound to class II major histocompatibility complex (MHC)-encoded molecules on the surface of antigen-presenting cells (APCs), for example B cells, macrophages, and dendritic cells. To induce maximal IL-2 production by T cells, however, APCs must also provide non-antigen-specific costimulatory signals. Recent work indicates that APC-derived costimulatory signals play a critical role in determining whether lymphokine production, apoptotic cell death, or functional anergy is induced by TCR engagement. This information has allowed immunologists to manipulate costimulatory molecules to prevent allograft rejection and enhance tumor immunity. Here we review current information on the biologic effects of, and signal transduction pathways engaged by, several known receptor-ligand pairs that transduce costimulatory signals in T cells. Special emphasis will be placed on the interaction of CD28 on the T cell with its ligands, B7-1, B7-2, and B7-3 on the APC.
单个抗原特异性CD4⁺T细胞克隆的激活及最终的克隆性扩增依赖于自分泌生长因子如白细胞介素-2（IL-2）的产生。CD4⁺T细胞激活的特异性是由T细胞抗原受体（TCR）识别与抗原呈递细胞（APC）表面II类主要组织相容性复合体（MHC）编码分子结合的肽抗原所赋予的，例如B细胞、巨噬细胞和树突状细胞。然而，为了诱导T细胞产生最大量的IL-2，APC还必须提供非抗原特异性的共刺激信号。最近的研究表明，APC衍生的共刺激信号在决定TCR结合是诱导淋巴因子产生、凋亡性细胞死亡还是功能性无反应性方面起着关键作用。这一信息使免疫学家能够操纵共刺激分子以预防同种异体移植排斥反应并增强肿瘤免疫。在此，我们综述了目前关于几种已知的在T细胞中传导共刺激信号的受体-配体对的生物学效应及所涉及的信号转导途径的信息。将特别强调T细胞上的CD28与其在APC上的配体B7-1、B7-2和B7-3之间的相互作用。
