Reactive oxygen species regulate activation-induced T cell apoptosis.
Reactive oxygen species (ROS) mediate apoptosis in a number of cell types. We studied the role that ROS play in activated T cell apoptosis by activating T cells in vivo and then culturing them for a short time. Activated T cells died independently of Fas and TNF alpha. Their death was characterized by rapid loss of mitochondrial transmembrane potential (delta psi(m)), caspase-dependent DNA fragmentation, and superoxide generation. A superoxide dismutase mimetic, Mn (III) tetrakis (5, 10, 15, 20-benzoic acid) porphyrin (MnTBAP), protected T cells from superoxide generation, caspase-dependent DNA loss, loss of delta psi(m), and cell death. These results indicate that ROS can regulate signals involved in caspase activation and apoptosis and may contribute to peripheral T cell deletion.
Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
D A
DA
Hildeman
T
T
Mitchell
T K
TK
Teague
P
P
Henson
B J
BJ
Day
J
J
Kappler
P C
PC
Marrack
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D020169:Caspases / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D007939:Leukemia L1210; D008213:Lymphocyte Activation / Q000187:drug effects; D008345:Manganese / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000502:physiology*; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000494:pharmacology
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D017382:Reactive Oxygen Species; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D008345:Manganese; D020169:Caspases