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Induction of apoptosis in mature T cells by tumour necrosis factor

Abstract

T-CELL receptor-induced apoptosis regulates immune responses and can result from interactions between Fas (Apol/CD95) and Fas ligand (FasL)1-12. Mutations in the genes for Fas and FasL cause disorders resembling human autoimmune diseases in lpr and gld mice, respectively13,14. However, peripheral T-cell deletion takes place in lpr mice, and autoimmune syndromes occur in mouse strains without Fas or FasL defects15,16. Here we show that tumour necrosis factor (TNF) can mediate mature T-cell receptor-induced apoptosis through the p75 TNF receptor. Blockage of both TNF and FasL is required to abrogate T-cell death and TNF mediates the death of most CD8+ T cells, whereas FasL mediates the death of most CD4+ T cells. Our results suggest that autoregulatory apoptosis of the mature T cells can occur by two distinct molecular mechanisms.

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Zheng, L., Fisher, G., Miller, R. et al. Induction of apoptosis in mature T cells by tumour necrosis factor. Nature 377, 348–351 (1995). https://doi.org/10.1038/377348a0

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