Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)
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.
Dhein
J
J
Tumorimmunology Program, German Cancer Research Center, Heidelberg.
Walczak
H
H
Bäumler
C
C
Debatin
K M
KM
Krammer
P H
PH
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D002460:Cell Line; D002999:Clone Cells; D017931:DNA Primers; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D019014:fas Receptor
D000954:Antigens, Surface; D017252:CD3 Complex; D017931:DNA Primers; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor