Muppidi Jagan R, Siegel Richard M
Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nat Immunol. 2004 Feb;5(2):182-9. doi: 10.1038/ni1024. Epub 2004 Jan 25.
Clonotypic elimination of activated T cells through Fas-Fas ligand (CD95-CD95L) interactions is one mechanism of peripheral self-tolerance. T cell receptor (TCR) stimuli trigger FasL synthesis but also sensitize activated T cells to Fas-mediated apoptosis through an unknown mechanism. Here we show that TCR restimulation of activated human CD4(+) T cells resulted in Fas translocation into lipid raft microdomains before binding FasL, rendering these cells sensitive to apoptosis after stimulation with bivalent antibody or FasL. Disruption of lipid rafts reduced sensitivity to Fas-mediated apoptosis after TCR restimulation. Thus, the redistribution of Fas and other tumor necrosis factor family receptors into and out of lipid rafts may dynamically regulate the efficiency and outcomes of signaling by these receptors.
通过Fas-Fas配体（CD95-CD95L）相互作用对活化T细胞进行克隆型清除是外周自身耐受的一种机制。T细胞受体（TCR）刺激可触发FasL合成，但也通过未知机制使活化的T细胞对Fas介导的凋亡敏感。我们在此表明，对活化的人CD4(+) T细胞进行TCR再刺激会导致Fas在与FasL结合之前转运到脂筏微结构域中，使这些细胞在用二价抗体或FasL刺激后对凋亡敏感。破坏脂筏会降低TCR再刺激后对Fas介导的凋亡的敏感性。因此，Fas和其他肿瘤坏死因子家族受体进出脂筏的重新分布可能动态调节这些受体信号传导的效率和结果。
