IL-7-regulated homeostatic maintenance of recent thymic emigrants in association with caspase-mediated cell proliferation and apoptotic cell death.
Homeostasis of T cells is essential to the maintenance of the T cell pool and TCR diversity. In this study, mechanisms involved in the regulation of cytokine-mediated expansion of naive T cells in the absence of Ag, in particular the role of caspase activation and susceptibility to apoptosis of recent thymic emigrants (RTEs), were examined. Low level caspase-8 and caspase-3 activation was detected in proliferating IL-7-treated cells in the absence of cell death during the first days of culture. Caspase inhibitors suppressed IL-7-induced expansion of RTEs. Low level expression of CD95 and blocking Ab experiments indicated that this early caspase activation was CD95 independent. However, CD95 levels subsequently became dramatically up-regulated on proliferating naive T cells, and these cells became susceptible to CD95 ligation, resulting in high level caspase activation and apoptotic cell death. These results show a dual role for caspases in proliferation and in CD95-induced cell death during Ag-independent expansion of RTEs. This method of cell death in IL-7-expanded RTEs is a previously unrecognized mechanism for the homeostatic control of expanded T cells.
O'Neill
Rose M
RM
Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland. Rmoneill@hotmail.com
Hassan
Jaythoon
J
Reen
Denis J
DJ
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D053222:Fas Ligand Protein; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007231:Infant, Newborn; D015851:Interleukin-7 / Q000502:physiology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015851:Interleukin-7; D008024:Ligands; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases