CD80 (B7-1) and CD86 (B7-2) are functionally equivalent in the initiation and maintenance of CD4+ T-cell proliferation after activation with suboptimal doses of PHA.
CD80 (B7-1) and CD86 (B7-2) are functionally equivalent in the initiation and maintenance of CD4+ T-cell proliferation after activation with suboptimal doses of PHA.
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DOI：
10.1089/10445490252925404
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发表时间：
2002-03
影响因子：
3.1
通讯作者：
V. Vasilevko;A. Ghochikyan;M. Holterman;M. Agadjanyan
中科院分区：
文献类型：
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作者：
V. Vasilevko;A. Ghochikyan;M. Holterman;M. Agadjanyan
T 细胞的有效激活需要两个独立的 T 细胞受体的结合。抗原特异性T细胞受体（TCR）结合外源肽抗原-MHC复合物，CD28受体结合抗原呈递细胞（APC）表面表达的B7（CD80/CD86）共刺激分子。这些 T 细胞表面受体及其特定配体的同时触发会导致该细胞的激活。相比之下，CTLA-4 (CD152) 是一种独特的 T 细胞受体，在与 B7 分子结合后，会向 T 细胞激活发送抑制信号。许多体外和体内研究表明，CD80 和 CD86 配体在 T 细胞激活中具有相同的作用。最近，在 B7-1 和/或 B7-2 敲除小鼠中研究了 B7 共刺激分子的体内功能，作者得出结论，CD86 对于启动 T 细胞反应可能更重要，而 CD80 对于维持这些免疫反应可能更重要。在这项研究中，我们直接比较了体外模式系统中CD80和CD86在启动和维持静息CD4+T细胞增殖中的作用，该系统允许通过使用次优剂量的PHA提供第一个信号效应细胞，并通过表达CD80或CD86的细胞提供第二个共刺激信号，但不提供任何其他共刺激分子。使用这个实验系统，我们证明CD80和CD86分子可以在静息CD4(+) T细胞的初始激活和维持其增殖反应中相互替代。
Effective activation of T cells requires engagement of two separate T-cell receptors. The antigen-specific T-cell receptor (TCR) binds foreign peptide antigen-MHC complexes, and the CD28 receptor binds to the B7 (CD80/CD86) costimulatory molecules expressed on the surface of antigen-presenting cells (APC). The simultaneous triggering of these T-cell surface receptors with their specific ligands results in an activation of this cell. In contrast, CTLA-4 (CD152) is a distinct T-cell receptor that, upon binding to B7 molecules, sends an inhibitory signal to T cell activation. Many in vitro and in vivo studies demonstrated that both CD80 and CD86 ligands have an identical role in the activation of T cells. Recently, functions of B7 costimulatory molecules in vivo have been investigated in B7-1 and/or B7-2 knockout mice, and the authors concluded that CD86 could be more important for initiating T-cell responses, while CD80 could be more significant for maintaining these immune responses. In this study, we directly compared the role of CD80 and CD86 in initiating and maintaining proliferation of resting CD4(+) T cells in an in vitro mode system that allowed to provide the first signal-to-effector cells through the use of suboptimal doses of PHA and the second costimulatory signal through cells expressing CD80 or CD86, but not any other costimulatory molecules. Using this experimental system we demonstrate that the CD80 and CD86 molecules can substitute for each other in the initial activation of resting CD4(+) T cells and in the maintenance of their proliferative response.