Strong TCR ligation without costimulation causes rapid onset of Fas-dependent apoptosis of naive murine CD4+ T cells.
Activation-induced cell death of T cells typically occurs late in the primary response after a prior proliferative response. Here, we describe a novel form of cell death in which purified naive murine CD4+ cells undergo apoptosis within 18 h in vitro after strong TCR ligation. Such rapid-onset TCR-mediated death of T cells does not involve cell division and is Fas-dependent, inhibited by CD28 (and IL-6) costimulation and enhanced by IL-4 and IL-7; by contrast, spontaneous death of CD4+ cells cultured alone is Fas-independent and inhibited by IL-4 and IL-7. TCR-mediated Fas-dependent death of CD4+ cells is prevented by combined TCR/Fas ligation and by drugs that inhibit calcineurin-dependent signaling and mitogen-activated protein kinase MEK1 activation.
Kishimoto
H
H
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sprent
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D053222:Fas Ligand Protein; D007156:Immunologic Memory; D016130:Immunophenotyping; D007424:Intracellular Fluid / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor