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

• Verfasst von: Dhein, Jens [VerfasserIn]
• Verfasst von: Walczak, Henning [VerfasserIn]
• Verfasst von: Bäumler, Caroline Beatrix [VerfasserIn]
• Verfasst von: Debatin, Klaus-Michael [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)
• Verf.angabe: Jens Dhein, Henning Walczak, Caroline Bäumler, Klaus-Michael Debatin, Peter H. Krammer
• E-Jahr: 1995
• Jahr: 02 February 1995
• Umfang: 4 S.
• Fussnoten: Gesehen am 17.09.2024
• Titel Quelle: Enthalten in: Nature
• Ort Quelle: London [u.a.] : Nature Publ. Group, 1869
• Jahr Quelle: 1995
• Band/Heft Quelle: 373(1995), 6513, Seite 438-441
• ISSN Quelle: 1476-4687
• DOI: doi:10.1038/373438a0
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Humanities and Social Sciences
• Sach-SW: multidisciplinary
• Sach-SW: Science
• K10plus-PPN: 1902730216

Abstract

THE APO-l/(Fas/CD95) cell surface receptor is a member of the nerve growth factor (NGF)/tumour necrosis factor (TNF) receptor superfamily and mediates apoptosis1 -4. Peripheral activated T cells (ATC) from lymphoproliferation (Ipr/lpr) mutant mice that express a reduced number of APO-1 receptors have a defect in T-cell receptor (TCR)-induced apoptosis5,6. This suggests that TCR-induced apoptosis involves APO-1. We tested this hypothesis in various human T cells: (1) malignant Jurkat cells, (2) an allo-reactive 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.