Oberg H H, Lengl-Janssen B, Robertson M J, Kabelitz D, Janssen O
Department of Immunology, Paul-Ehrlich-Institute, D63225 Langen, Germany.
Cell Death Differ. 1997 Jul;4(5):403-12. doi: 10.1038/sj.cdd.4400256.
Activated T cells undergo apoptosis when the Fas-antigen (APO-1, CD95) is ligated by Fas Ligand (FasL) or agonistic anti-Fas antibodies. Repeated stimulation of T lymphocytes via the TCR/CD3-complex induces activation-induced cell death (AICD) associated with FasL surface expression. FasL binding to Fas molecules triggers the Fas-dependent death signaling cascade. Since it is still controversial whether Fas-induced cell death is associated with tyrosine kinase activity, we investigated the tyrosine kinase activation requirements in anti-Fas antibody-induced cell death and AICD in human T cell clones. We report that cell death triggered by anti-Fas antibody is not accompanied by an increase in tyrosine phosphorylation and cannot be blocked by inhibitors of protein tyrosine kinases (PTK). Under the same conditions, AICD of T cell clones is clearly associated with tyrosine kinase activation. In fact, semiquantitative RT-PCR analysis of FasL mRNA expression triggered in T cell clones via the TCR/CD3-complex revealed that tyrosine phosphorylation is required for functional FasL mRNA and surface expression.
当Fas抗原（APO-1，CD95）与Fas配体（FasL）或抗Fas激动性抗体结合时，活化的T细胞会发生凋亡。通过TCR/CD3复合物反复刺激T淋巴细胞会诱导与FasL表面表达相关的活化诱导细胞死亡（AICD）。FasL与Fas分子的结合触发了Fas依赖性死亡信号级联反应。由于Fas诱导的细胞死亡是否与酪氨酸激酶活性相关仍存在争议，我们研究了抗Fas抗体诱导的细胞死亡和人T细胞克隆中AICD的酪氨酸激酶激活需求。我们报告，抗Fas抗体触发的细胞死亡不会伴随着酪氨酸磷酸化的增加，并且不能被蛋白酪氨酸激酶（PTK）抑制剂阻断。在相同条件下，T细胞克隆的AICD明显与酪氨酸激酶激活相关。事实上，通过TCR/CD3复合物在T细胞克隆中触发的FasL mRNA表达的半定量RT-PCR分析表明，功能性FasL mRNA和表面表达需要酪氨酸磷酸化。
