Müller K P, Mariani S M, Matiba B, Kyewski B, Krammer P H
Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
Eur J Immunol. 1995 Oct;25(10):2996-9. doi: 10.1002/eji.1830251043.
The CD95 (APO-1/Fas) ligand (CD95L) mediates apoptosis in sensitive target cells, Ca(2+)-independent cytotoxicity of cells from perforin knock-out mice, and peripheral deletion of activated T cells through engagement of its cognate receptor CD95. Double-positive thymocytes show a high constitutive expression of CD95. Therefore, we used a model system and investigated whether negative selection through apoptosis might involve CD95/CD95L. We analyzed whether CD95L may induce antigen-specific deletion of double-positive thymocytes from mice transgenic for a lymphocytic choriomeningitis virus (LCMV)/H2b-specific T cell receptor (TCR). These cells are deleted in vitro upon addition of the LCMV-peptide 33-41 in a major histocompatibility complex-class I-restricted fashion. Deletion was not blocked by soluble mouse and human CD95-Fc receptor decoys. CD95-Fc receptor decoys, however, were effective in blocking apoptosis induced by mouse CD95L-transfected L929 cells in sensitive CD95+ target cells and in thymocytes. These results suggest that TCR-induced deletion of immature thymocytes in vitro is independent of CD95L. Thus, our data argue against a role of CD95L in negative selection of MHC-class I-restricted autoreactive thymocytes.
CD95（APO-1/Fas）配体（CD95L）介导敏感靶细胞的凋亡、穿孔素基因敲除小鼠细胞的钙离子非依赖性细胞毒性以及通过其同源受体CD95的结合实现活化T细胞的外周清除。双阳性胸腺细胞呈现出较高的CD95组成性表达。因此，我们使用了一个模型系统来研究通过凋亡进行的阴性选择是否涉及CD95/CD95L。我们分析了CD95L是否可能诱导来自淋巴细胞性脉络丛脑膜炎病毒（LCMV）/H2b特异性T细胞受体（TCR）转基因小鼠的双阳性胸腺细胞发生抗原特异性清除。在体外加入LCMV肽33 - 41后，这些细胞以主要组织相容性复合体I类限制的方式被清除。可溶性小鼠和人CD95-Fc受体诱饵并不能阻断这种清除。然而，CD95-Fc受体诱饵能够有效阻断小鼠CD95L转染的L929细胞在敏感的CD95+靶细胞和胸腺细胞中诱导的凋亡。这些结果表明，体外TCR诱导的未成熟胸腺细胞清除独立于CD95L。因此，我们的数据表明CD95L在MHC I类限制性自身反应性胸腺细胞的阴性选择中不起作用。
