Regulation of programmed cell death following T cell activation in vivo.
Activation of T cell hybridomas in vitro induces rapid Fas-Fas ligand (FasL)-mediated programmed cell death (apoptosis). In contrast, T cells activated by antigen or superantigen in vivo undergo a population expansion and then decline due to Fas-FasL-mediated activation-induced apoptosis (AIA). We asked how T cells activated by antigen in vivo proliferated before undergoing apoptosis. Two possibilities were analyzed: either (i) the apoptosis program was not 'turned on' or (ii) was 'blocked' during the period of cellular proliferation in vivo. Data presented in this manuscript support the second of these possibilities. CD4+ T cells activated in vivo were resistant to anti-fas-mediated apoptosis until 48 h following staphylococcal enterotoxin B (SEB) administration, despite the fact that activated proliferating T cells expressed high levels of Fas (CD95) antigen and many 'apoptosis genes' were induced within 24 h of SEB administration. The analysis of the expression patterns of 'apoptosis genes' during the T cell activation further suggested that temporal blockade of AIA may be due to the induction of apoptosis-preventing genes, such as bag-1.
Yang
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Department of Medicine, Stanford University School of Medicine, CA 94305-5111, USA.
Kim
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Fathman
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CG
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D053222:Fas Ligand Protein; D015870:Gene Expression; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D019014:fas Receptor / Q000378:metabolism
C091732:BCL2-associated athanogene 1 protein; C494820:Bad protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal; D007041:Hypoxanthine Phosphoribosyltransferase