Caspases in T-cell receptor-induced thymocyte apoptosis.
Apoptosis eliminates inappropriate or autoreactive T lymphocytes during thymic development. Intracellular mediators involved in T-cell receptor (TCR)-mediated apoptosis in developing thymocytes during negative selection are therefore of great interest. Caspases, cysteine proteases that mediate mature T-cell apoptosis, have been implicated in thymocyte cell death, but their regulation is not understood. We examined caspase activities in distinct thymocyte subpopulations that represent different stages of T-cell development. We found caspase activity in CD4+CD8+ double positive (DP) thymocytes, where selection involving apoptosis occurs. Earlier and later thymocyte stages exhibited no caspase activity. Only certain caspases, such as caspase-3 and caspase-8-like proteases, but not caspase-1, are active in DP thymocytes in vivo and can be activated when DP thymocytes are induced to undergo apoptosis in vitro by TCR-crosslinking. Thus, specific caspases appear to be developmentally regulated in thymocytes.
Jiang
D
D
Molecular Development of the Immune System Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892, USA.
Zheng
L
L
Lenardo
M J
MJ
D000818:Animals; D017209:Apoptosis; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D053455:Caspase 10; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology
D018106:CD28 Antigens; D017252:CD3 Complex; D015853:Cysteine Proteinase Inhibitors; D011948:Receptors, Antigen, T-Cell; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053455:Caspase 10; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1; C506438:CASP10 protein, human