Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement
Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement
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DOI：
10.1016/s1074-7613(00)80284-8
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发表时间：
1997-04-01
期刊：
影响因子：
32.4
通讯作者：
Abbas, AK
中科院分区：
文献类型：
--
作者：
Perez, VL;VanParijs, L;Abbas, AK
对体外T细胞能量的研究已经导致了广泛接受的观点，即能量是由T细胞抗原识别诱导的，没有共刺激。我们发现，体内T细胞能量的诱导是由于需要识别B7分子的T细胞反应失败，因为阻断B7使T细胞处于未激活但功能正常的状态。此外，通过阻断CTLA-4 （B7分子的抑制性T细胞受体）来阻止能量的诱导。因此，体内T细胞能量的诱导可能不是由于缺乏共刺激，而是由于CTLA-4对B7分子的特异性识别。相反，阻断T细胞上的CD28可以阻止启动，但不能诱导耐受性。因此，T细胞对抗原的识别结果取决于CD28或CTLA-4在T细胞上与B7分子的相互作用。
Studies of T cell anergy in vitro have led to the widely accepted view that anergy is induced by T cell antigen recognition without costimulation. We show that the induction of T cell anergy in vivo is due to an abortive T eel response that requires recognition of B7 molecules, since blocking B7 maintains T cells in an unactivated but functionally competent state. Furthermore, the induction of anergy is prevented by blocking CTLA-4, the inhibitory T cell receptor for B7 molecules. Thus, in vivo T cell anergy may be induced not because of a lack of costimulation, but as a result of specific recognition of B7 molecules by CTLA-4. In contrast, blocking CD28 on T cells prevents priming but not the induction of tolerance. Therefore, the outcome of antigen recognition by T cells is determined by the interaction of CD28 or CTLA-4 on the T cells with B7 molecules.