Fas (CD95)-independent regulation of immune responses by antigen-specific CD4-CD8+ T cells.
Antigen-activated T cells of the CD4(+)CD8(-) phenotype are susceptible to antigen receptor-stimulated cell death. This form of apoptotic cell death has been shown to be dependent on the expression of the Fas (CD95) antigen and can occur via an autocrine mechanism involving the concomitant up-regulation of Fas and its ligand on activated T cells. Mutation in genes encoding Fas (Ipr) and the Fas ligand (gld) contribute to the development of an autoimmune syndrome similar to systemic lupus erythematosus in mice. These observations led to the suggestion that the Fas signaling pathway is an important regulator of immune responses in vivo. Here we evaluated the importance of the Fas pathway in regulating immune responses by male antigen-specific CD4(-)CD8(+) T cells. We found that the in vivo elimination of these activated cells was independent of Fas expression by these cells. However, the elimination of these activated cells was inhibited by the transgenic expression of Bcl-2, a protein that inhibits multiple forms of apoptotic cell death. The transgenic Bcl-2 protein also inhibited the death of male antigen-activated cells following IL-2 deprivation. Cell death resulting from IL-2 deprivation occurred efficiently in male antigen-activated Fas- cells. We propose that the rapid deletion of male antigen-activated Fas- cells in vivo is due to limiting amounts of IL-2 that are available in the microenvironment of the activated cells at the peak of the response.
Teh
S J
SJ
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Dutz
J P
JP
Motyka
B
B
Teh
H S
HS
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion; D053222:Fas Ligand Protein; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006182:H-Y Antigen; D007376:Interleukin-2; D008024:Ligands; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D011505:Protein-Tyrosine Kinases