title: The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance.
abstract: Using cells from TCR transgenic mice that do or do not express Fas, we show that there are two mechanistically distinct forms of apoptosis in CD4+ T cells. Naive T cells undergo apoptosis if cultured in the absence of antigen or costimulation. This form of programmed cell death (PCD) is not dependent on Fas, and is prevented by CD28-mediated signals, which lead to the secretion of growth factors and the expression of survival genes, such as bcl-xL. Recently activated T cells undergo apoptotic death upon repeated stimulation. This activation-induced cell death (AICD) is mediated by Fas, but is independent of costimulation and is not prevented by IL-2 or bcl-xL. Finally, we show that peripheral tolerance may be induced in vivo independent of Fas-mediated cell death.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: L
authors.initials: L
authors.lastname: Van Parijs
authors.forename: A
authors.initials: A
authors.lastname: Ibraghimov
authors.forename: A K
authors.initials: AK
authors.lastname: Abbas
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D017209:Apoptosis / Q000276:immunology*; D018106:CD28 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011519:Proto-Oncogenes / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
chemical_list: D018106:CD28 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor