Klas C, Debatin K M, Jonker R R, Krammer P H
Tumorimmunology Program, German Cancer Research Center, Heidelberg.
Int Immunol. 1993 Jun;5(6):625-30. doi: 10.1093/intimm/5.6.625.
One of the mechanisms to terminate a specific immune response may involve elimination of antigen activated T cells by programmed cell death, apoptosis. Apoptosis in activated T cells may be induced via the TCR-CD3 complex or/and cell surface molecules like the APO-1 (Fas) antigen, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily. To investigate apoptosis in activated T cells we studied expression of APO-1 and sensitivity to APO-1 mediated apoptosis in human peripheral T lymphocytes. APO-1 is not expressed on cord blood and the majority of resting T cells, but on activated T cells. One day activated T cells in culture showed activation induced resistance to apoptosis (ARA). However, after prolonged in vitro culture, 6 day activated T cells acquired sensitivity to activation induced sensitivity to apoptosis (ASA). Restimulation of the ASA+ activated T cells by triggering TCR-CD3 or CD2 induced proliferation and apoptosis in a fraction of the cells. In the surviving fraction of ASA+ activated T cells, however, this treatment reinduced a transient ARA+ phenotype. Thus, activation of resting mature T cells or restimulation of activated T cells may induce a transient resistance to apoptotic signals. Activation signals may interfere with the APO-1 pathway and may prevent elimination of activated T cells in the periphery (peripheral selection).
终止特定免疫反应的机制之一可能涉及通过程序性细胞死亡即凋亡来清除抗原激活的T细胞。激活的T细胞中的凋亡可能通过TCR-CD3复合物或/和细胞表面分子如APO-1（Fas）抗原诱导，APO-1是神经生长因子/肿瘤坏死因子受体超家族的新成员。为了研究激活的T细胞中的凋亡，我们研究了人外周血T淋巴细胞中APO-1的表达以及对APO-1介导的凋亡的敏感性。APO-1在脐血和大多数静止T细胞上不表达，但在激活的T细胞上表达。培养一天的激活T细胞表现出激活诱导的凋亡抗性（ARA）。然而，经过长时间体外培养后，培养6天的激活T细胞获得了对激活诱导的凋亡敏感性（ASA）。通过触发TCR-CD3或CD2对ASA+激活T细胞进行再次刺激，可诱导一部分细胞增殖和凋亡。然而，在ASA+激活T细胞的存活部分中，这种处理会再次诱导出短暂的ARA+表型。因此，静止成熟T细胞的激活或激活T细胞的再次刺激可能诱导对凋亡信号的短暂抗性。激活信号可能干扰APO-1途径，并可能阻止外周激活T细胞的清除（外周选择）。
