Induction of apoptosis in mature T cells by tumour necrosis factor

Nature. 1995 Sep 28;377(6547):348-51. doi: 10.1038/377348a0.


T-cell receptor-induced apoptosis regulates immune responses and can result from interactions between Fas (Apo1/CD95) and Fas ligand (FasL). Mutations in the genes for Fas and FasL cause disorders resembling human autoimmune diseases in lpr and gld mice, respectively. However, peripheral T-cell deletion takes place in lpr mice, and autoimmune syndromes occur in mouse strains without Fas or FasL defects. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line
  • Fas Ligand Protein
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Tumor Necrosis Factor / physiology
  • T-Lymphocytes / physiology*
  • Tumor Necrosis Factor-alpha / deficiency
  • Tumor Necrosis Factor-alpha / physiology*


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha