Activation-induced T cell death: Resistance or susceptibility correlate with cell surface Fas ligand expression and T helper phenotype
Activation-induced T cell death: Resistance or susceptibility correlate with cell surface Fas ligand expression and T helper phenotype
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DOI：
10.1006/cimm.1997.1200
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发表时间：
1997-10-10
影响因子：
4.3
通讯作者：
Janssen, O
中科院分区：
文献类型：
--
作者：
Oberg, HH;LenglJanssen, B;Janssen, O
当Fas-抗原（Apo-1，CD 95）被Fas配体分子（FasL）或激动性抗Fas抗体连接时，活化的T细胞经历凋亡。通过TCR/CD 3复合物再刺激T淋巴细胞诱导活化诱导的细胞死亡（AICD）。AICD和Fas诱导的细胞死亡是因果相关的，因为TCR诱导的AICD至少部分取决于Fas/FasL相互作用。因此，T细胞的再刺激导致FasL基因转录和表面表达。然后，膜结合或分泌的FasL分子与同一细胞或相邻细胞上的Fas受体结合，以触发死亡信号级联反应。我们比较了Fas介导的细胞凋亡和AICD在一组人T细胞克隆。虽然所有克隆都被抗Fas mAb杀死，但一些克隆对由抗TCR/CD 3 mAb或超抗原触发的AICD具有抗性。TCR诱导的蛋白质酪氨酸磷酸化的模式在AICD耐药和易感克隆中是可比的，因为是FasL mRNA的诱导。然而，在AICD敏感克隆中诱导的FasL表面表达水平上观察到显著差异，而在AICD抗性克隆中没有。CD 3刺激的克隆细胞的细胞因子谱支持最近的观察，AICD的敏感性仅限于Th 1亚群。然而，AICD抗性不仅与经典的Th 2表型相关。(C)北京：科学出版社.
Activated T cells undergo apoptosis when the Fas-antigen (Apo-1, CD95) is ligated by Fas ligand molecules (FasL) or agonistic anti-Fas antibodies. Restimulation of T lymphocytes via the TCR/CD3 complex induces activation-induced cell death (AICD). AICD and Fas-induced cell death are causally related since TCR-induced AICD at least in part depends on Fas/FasL interactions. Thus, restimulation of T cells leads to FasL gene transcription and surface expression. Membrane-bound or secreted FasL molecules then bind to Fas receptors on the same cell or on a neighbor cell to trigger the death signaling cascade. We have compared Fas-mediated apoptosis and AICD in a panel of human T cell clones. While all clones were killed by anti-Fas mAb, several clones were resistant to AICD triggered by anti-TCR/CD3 mAb or superantigen. The pattern of TCR-induced protein tyrosine phosphorylation was comparable in AICD-resistant and -susceptible clones, as was the induction of FasL mRNA. However, significant differences were observed at the level of FasL surface expression which was induced in AICD-susceptible but not in AICD-resistant clones. Cytokine profiles of CD3-stimulated clone cells support the recent observations that AICD sensitivity is restricted to the Th1 subset. However, AICD-resistance is not only associated with the classical Th2 phenotype. (C) 1997 Academic Press.