A protease-dependent TCR-induced death pathway in mature lymphocytes.
Several cysteine and serine protease inhibitors previously shown to block TCR-induced death of 2B4 T hybridoma cells were tested for their ability to block various T lymphocyte apoptotic death systems. TCR-induced death of both peripheral CD4+ and CD8+ T cell blasts was inhibited similarly to the hybridoma, but cell death in these cells induced by anti-Fas, gamma-irradiation, etoposide, or extracellular ATP was not blocked. For T cell lines, cell death induced by CTL or by IL-2 withdrawal was also not inhibited. TCR-induced death of immature CD+8+ thymocytes triggered by culture on immobilized anti-CD3 was not blocked by these protease inhibitors, whereas similar death induced in the resting CD4+8- thymocyte subset under these conditions was inhibited similarly to the T cell blasts. TCR-induced proliferation of the latter subset was modest in the absence of exogeneous IL-2, but was enhanced two- to fourfold by the protease inhibitors. These results show that a protease-dependent death pathway can be triggered by the TCR in mature T cells; similar protease-dependent steps are not common to the TCR-triggered activation pathway or other apoptotic death pathways in these cells.
Sarin
A
A
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nakajima
H
H
Henkart
P A
PA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002154:Calpain / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D010450:Endopeptidases / Q000502:physiology*; D007976:Leupeptins / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D000911:Antibodies, Monoclonal; D007976:Leupeptins; D011480:Protease Inhibitors; D011948:Receptors, Antigen, T-Cell; D010450:Endopeptidases; D002154:Calpain; C032854:leupeptin