The Fas/Fas ligand pathway and Bcl-2 regulate T cell responses to model self and foreign antigens.
We have examined the role of Fas and Bcl-2 in T cell survival and responses to antigen in vivo using T cells that express a transgenic antigen receptor specific for hen egg lysozyme (HEL) and that either lack functional Fas or Fas ligand (FasL) or overexpress Bcl-2 as a transgene. HEL-specific, Bcl-2-transgenic T cells showed prolonged responses to immunization with cognate peptide but were eliminated rapidly when exposed to HEL expressed systemically as a self antigen. In contrast, Fas- and FasL-defective T cells did not display exaggerated responses to immunization with HEL peptide, but did show increased expansion and survival in response to systemic self antigen and were able to activate anti-HEL (self) antibody-forming cells. Thus, Bcl-2 and Fas play different roles in the regulation of T cell responses to antigen in vivo and in self tolerance.
Van Parijs
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Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Peterson
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D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D006706:Homeostasis; D007108:Immune Tolerance; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D001323:Autoantibodies; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; C066759:hen egg lysozyme peptide (46-61); D009113:Muramidase