title: Caspase activation is required for T cell proliferation.
abstract: Triggering of Fas (CD95) by its ligand (FasL) rapidly induces cell death via recruitment of the adaptor protein Fas-associated death domain (FADD), resulting in activation of a caspase cascade. It was thus surprising that T lymphocytes deficient in FADD were reported recently to be not only resistant to FasL-mediated apoptosis, but also defective in their proliferative capacity. This finding suggested potentially dual roles of cell growth and death for Fas and possibly other death receptors. We report here that CD3-induced proliferation and interleukin 2 production by human T cells are blocked by inhibitors of caspase activity. This is paralleled by rapid cleavage of caspase-8 after CD3 stimulation, but no detectable processing of caspase-3 during the same interval. The caspase contribution to T cell activation may occur via TCR-mediated upregulation of FasL, as Fas-Fc blocked T cell proliferation, whereas soluble FasL augmented CD3-induced proliferation. These findings extend the role of death receptors to the promotion of T cell growth in a caspase-dependent manner.
authors.affiliation: Immunobiology Program, Department of Medicine, The University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Kennedy
authors.forename: T
authors.initials: T
authors.lastname: Kataoka
authors.forename: J
authors.initials: J
authors.lastname: Tschopp
authors.forename: R C
authors.initials: RC
authors.lastname: Budd
mesh_terms: D017252:CD3 Complex / Q000276:immunology; D020169:Caspases / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D020169:Caspases