The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice.
The role of a cell death-associated gene, fas, in T lymphocyte development and responses to antigen has been analyzed by breeding a transgenic T cell receptor specific for the 81-104 peptide of pigeon cytochrome c into fas-defective MRL-lpr/lpr and control MRL+/+ mice. Transgene-expressing T cells mature normally in both strains and populate peripheral lymphoid tissues in normal numbers. Mature CD4+ T cells from the lpr/lpr mice are resistant to suppression by high doses of antigen and to apoptotic cell death. In vivo administration of peptide antigen causes deletion of thymic T cells in both MRL-lpr/lpr and MRL+/+ strains. By contrast, antigen-induced deletion of peripheral T cells occurs in the MRL+/+ but not in the MRL-lpr/lpr strain. Therefore, the fas gene plays an essential role in activation-induced cell death in mature T lymphocytes, but not in the negative selection of immature cells in the thymus.
Singer
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GG
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Abbas
A K
AK
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000648:ultrastructure*; D016922:Cellular Senescence; D017353:Gene Deletion; D015870:Gene Expression; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D019014:fas Receptor
D000954:Antigens, Surface; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor