Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)

Nature. 1995 Feb 2;373(6513):438-41. doi: 10.1038/373438a0.


The APO-1/(Fas/CD95) cell surface receptor is a member of the nerve growth factor (NGF)/tumour necrosis factor (TNF) receptor superfamily and mediates apoptosis. Peripheral activated T cells (ATC) from lymphoproliferation (lpr/lpr) mutant mice that express a reduced number of APO-1 receptors have a defect in T-cell receptor (TCR)-induced apoptosis. This suggests that TCR-induced apoptosis involves APO-1. We tested this hypothesis in various human T cells: (1) malignant Jurkat cells, (2) an alloreactive T-cell clone (S13), and (3) peripheral ATC. TCR triggering through immobilized anti-CD3 antibodies or Staphylococcus enterotoxin B (SEB) superantigen induced expression of the APO-1 ligand and apoptosis in these cells. Anti-CD3-induced apoptosis of Jurkat cells was demonstrated even in single-cell cultures. In all cases apoptosis was substantially inhibited by blocking anti-APO-1 antibody fragments and soluble APO-1 receptor decoys. The APO-1 ligand was found in the supernatant of activated Jurkat cells as a soluble cytokine. We propose that TCR-induced apoptosis in ATC can occur through an APO-1 ligand-mediated autocrine suicide. These results provide a mechanism for suppression of the immune response and for peripheral tolerance by T-cell deletion.

MeSH terms

  • Animals
  • Antigens, Surface / immunology
  • Antigens, Surface / physiology*
  • Apoptosis / physiology*
  • Base Sequence
  • CD3 Complex / immunology
  • CD3 Complex / physiology
  • Cell Line
  • Clone Cells
  • DNA Primers
  • Humans
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / physiology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • fas Receptor


  • Antigens, Surface
  • CD3 Complex
  • DNA Primers
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • fas Receptor