Peter M E, Dhein J, Ehret A, Hellbardt S, Walczak H, Moldenhauer G, Krammer P H
Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
Int Immunol. 1995 Nov;7(11):1873-7. doi: 10.1093/intimm/7.11.1873.
Certain B and T cell lines respond to activation signals, e.g. through the antigen receptor, by undergoing apoptotic cell death. In T cells it has been recently shown that TCR-mediated apoptosis involves APO-1/Fas(CD95) receptor-ligand interaction. To investigate whether the TCR-CD3 complex can trigger alternative apoptosis pathways we generated subclones of the T cell line Jurkat which were completely resistant towards APO-1-mediated apoptosis. These JurkatR cells differed phenotypically from sensitive parental JurkatS cells only by the lack of APO-1 protein expression. Although JurkatR cells responded normally to anti-CD3 stimulation by expression of APO-1 ligand they failed to undergo anti-CD3-induced apoptosis. Thus, in Jurkat cells APO-1-mediated apoptosis was the main, and might be the only, mechanism for anti-CD3-induced cell death. However, BL-60 B cells, highly sensitive to anti-IgM-induced apoptosis, did not use the APO-1 receptor-ligand system because they failed to express APO-1 ligand mRNA. Taken together, our results suggest that malignant T and B cell lines may use APO-1 receptor-ligand-dependent and -independent antigen receptor-induced apoptosis pathways respectively. Similarly, differential pathways may be used by T and B cell subsets.
某些B细胞和T细胞系会通过抗原受体等激活信号，经历凋亡性细胞死亡来对激活信号作出反应。最近在T细胞中发现，TCR介导的凋亡涉及APO-1/Fas(CD95)受体-配体相互作用。为了研究TCR-CD3复合物是否能触发其他凋亡途径，我们构建了对APO-1介导的凋亡完全抗性的T细胞系Jurkat的亚克隆。这些JurkatR细胞与敏感的亲代JurkatS细胞在表型上的差异仅在于缺乏APO-1蛋白表达。尽管JurkatR细胞通过表达APO-1配体对抗CD3刺激有正常反应，但它们未能经历抗CD3诱导的凋亡。因此，在Jurkat细胞中，APO-1介导的凋亡是抗CD3诱导细胞死亡的主要机制，可能也是唯一机制。然而，对抗IgM诱导的凋亡高度敏感的BL-60 B细胞并不使用APO-1受体-配体系统，因为它们未能表达APO-1配体mRNA。综上所述，我们的结果表明，恶性T细胞系和B细胞系可能分别使用依赖和不依赖APO-1受体-配体的抗原受体诱导凋亡途径。同样，T细胞亚群和B细胞亚群可能使用不同的途径。
