Hornung F, Zheng L, Lenardo M J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
J Immunol. 1997 Oct 15;159(8):3816-22.
Ag-induced mature T cell apoptosis is the result of death-inducing cytokines, including the ligand for CD95 (Apo-1/Fas). This raises the possibility that expression of this death molecule could affect bystander T cells that were not directly antigenically stimulated but that express the CD95 receptor. We show here that bystander T cells, even if they express the CD95 receptor, are not killed when exposed to T cells undergoing Ag-induced apoptosis. Rather, cell death is restricted to T cells that bear the receptor clonotype that is specifically engaged by TCR ligands. At least one mechanism of clonotype restriction is a significant enhancement of CD95-induced apoptosis by TCR ligation. Our results demonstrate that, in addition to the well-known ability of TCR to stimulate apoptosis by inducing CD95 ligand expression, TCR signals at the time of CD95 engagement can effectively increase apoptosis. Therefore, we put forward the hypothesis that strict clonotype specificity is preserved when death cytokines such as CD95 ligand induce autoregulatory mature T cell apoptosis, at least in part through a sensitization signal provided by the TCR stimulation.
抗原诱导的成熟T细胞凋亡是包括CD95（Apo-1/Fas）配体在内的死亡诱导细胞因子作用的结果。这就提出了一种可能性，即这种死亡分子的表达可能会影响未直接受到抗原刺激但表达CD95受体的旁观者T细胞。我们在此表明，旁观者T细胞即使表达CD95受体，在暴露于经历抗原诱导凋亡的T细胞时也不会被杀死。相反，细胞死亡仅限于携带与TCR配体特异性结合的受体克隆型的T细胞。克隆型限制的至少一种机制是TCR连接显著增强CD95诱导的凋亡。我们的结果表明，除了TCR通过诱导CD95配体表达来刺激凋亡这一众所周知的能力外，CD95结合时的TCR信号可有效增加凋亡。因此，我们提出这样一个假说：当诸如CD95配体等死亡细胞因子诱导自身调节性成熟T细胞凋亡时，至少部分是通过TCR刺激提供的致敏信号来保持严格的克隆型特异性。
