CTLA-4 CAN FUNCTION AS A NEGATIVE REGULATOR OF T-CELL ACTIVATION
CTLA-4 CAN FUNCTION AS A NEGATIVE REGULATOR OF T-CELL ACTIVATION
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DOI：
10.1016/1074-7613(94)90071-x
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发表时间：
1994-08-01
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：
WALUNAS, TL;LENSCHOW, DJ;BLUESTONE, JA
CD 28和CTLA-4是在T细胞上发现的相关糖蛋白。抗原受体结合后CD 28的连接提供了T细胞活化所需的共刺激信号。产生抗CTLA-4抗体以检查CTLA-4受体对鼠T细胞的作用。作为同源二聚体的CTLA-4的表达在T细胞活化后2-3天上调。抗CTLA-4抗体和Fab片段增强同种异体MLR中的T细胞增殖。然而，当存在最佳共刺激和Fc交联时，抗CTLA-4单克隆抗体抑制T细胞增殖。总之，这些结果表明MAb可能阻碍CTLA-4与其天然配体的相互作用并阻断负信号，或直接向T细胞发出信号以下调免疫功能。
CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor on murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 MAbs inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function.