AUTOCRINE T-CELL SUICIDE MEDIATED BY APO-1/(FAS/CD95)
AUTOCRINE T-CELL SUICIDE MEDIATED BY APO-1/(FAS/CD95)
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DOI：
10.1038/373438a0
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发表时间：
1995-02-02
期刊：
影响因子：
64.8
通讯作者：
KRAMMER, PH
中科院分区：
文献类型：
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作者：
DHEIN, J;WALCZAK, H;KRAMMER, PH
APO - 1/（Fas/CD95）细胞表面受体是神经生长因子（NGF）/肿瘤坏死因子（TNF）受体超家族的成员，并介导细胞凋亡（1 - 4）。来自淋巴细胞增殖（lpr/lpr）突变小鼠的外周活化T细胞（ATC）表达的APO - 1受体数量减少，其在T细胞受体（TCR）诱导的细胞凋亡方面存在缺陷（5,6）。这表明TCR诱导的细胞凋亡涉及APO - 1。我们在各种人类T细胞中检验了这一假设：（1）恶性Jurkat细胞，（2）同种反应性T细胞克隆（S13），以及（3）外周ATC。通过固定化的抗CD3抗体或葡萄球菌肠毒素B（SEB）超抗原触发TCR，可诱导这些细胞中APO - 1配体的表达和细胞凋亡。即使在单细胞培养中，也证实了抗CD3诱导的Jurkat细胞凋亡。在所有情况下，阻断性抗APO - 1抗体片段和可溶性APO - 1受体诱饵都可显著抑制细胞凋亡。在活化的Jurkat细胞上清液中发现APO - 1配体是一种可溶性细胞因子。我们提出，ATC中TCR诱导的细胞凋亡可通过APO - 1配体介导的自分泌自杀发生。这些结果为免疫应答的抑制以及通过T细胞缺失产生外周耐受提供了一种机制。
THE APO-1/(Fas/CD95) cell surface receptor is a member of the nerve growth factor (NGF)/tumour necrosis factor (TNF) receptor superfamily and mediates apoptosis(1-4). Peripheral activated T cells (ATC) from lymphoproliferation (lpr/lpr) mutant mice that express a reduced number of APO-1 receptors have a defect in T-cell receptor (TCR)-induced apoptosis(5,6). This suggests that TCR-induced apoptosis involves APO-1. We tested this hypothesis in various human T cells: (1) malignant Jurkat cells, (2) an alloreactive T-cell clone (S13), and (3) peripheral ATC. TCR triggering through immobilized anti-CD3 antibodies or Staphylococcus enterotoxin B (SEB) superantigen induced expression of the APO-1 ligand and apoptosis in these cells. Anti-CD3-induced apoptosis of Jurkat cells was demonstrated even in single-cell cultures. In all cases apoptosis was substantially inhibited by blocking anti-APO-1 antibody fragments and soluble APO-I receptor decoys. The APO-1 ligand was found in the supernatant of activated Jurkat cells as a soluble cytokine. We propose that TCR-induced apoptosis in ATC can occur through an APO-1 ligand-mediated autocrine suicide. These results provide a mechanism for suppression of the immune response and for peripheral tolerance by T-cell deletion.