title: A role for Fas in negative selection of thymocytes in vivo.
abstract: To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1-100 microg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vbeta8+ cells at the level of the semi-mature population of HSAhi CD4+ 8- cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vbeta8+ HSAhi CD4+ 8- thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (</=1 microg) but not by high doses (100 microg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.
authors.affiliation: Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kishimoto
authors.forename: C D
authors.initials: CD
authors.lastname: Surh
authors.forename: J
authors.initials: J
authors.lastname: Sprent
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013950:Thymus Gland / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal; D010047:Ovalbumin