Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim.
At the end of the T cell response, the majority of the activated T cells die. We activated Vbeta8(+) T cells with staphylococcal enterotoxin B (SEB) in vivo and monitored the expansion and deletion of Vbeta8(+) T cells. We found that, in response to SEB, activated T cells died in vivo in the absence of Fas or TNF-R signaling but not when they overexpressed human Bcl-2. We also found that Vbeta8(+) T cells from Bim-deficient mice are resistant to SEB-induced deletion. While Bim levels did not change, endogenous Bcl-2 levels within Vbeta8(+) T cells decrease following SEB injection. Thus, the death of superantigen-stimulated T cells in vivo is mediated by Bim and may be modulated by a decrease in Bcl-2.
Howard Hughes Medical Institute and Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA. david.hildeman@chmcc.org
David A
DA
Hildeman
Yanan
Y
Zhu
Thomas C
TC
Mitchell
Philippe
P
Bouillet
Andreas
A
Strasser
John
J
Kappler
Philippa
P
Marrack
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D004768:Enterotoxins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018124:Receptors, Tumor Necrosis Factor; D018089:Superantigens; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal