title: gld/gld mice are unable to express a functional ligand for Fas.
abstract: Mice homozygous for either the lpr or gld genes develop phenotypically identical autoimmune disorders. The gene responsible for the pathology in lpr/lpr mice encodes the Fas antigen, a protein associated with the induction of programmed cell death. To determine if the defect associated with gld represents a mutation in the ligand for Fas, we have assessed the ability of lymphoid cells from homozygous gld/gld mice to lyse target cells in a Fas-dependent manner. Using an antagonistic antibody to Fas, we demonstrate that activated T cells from normal and lpr mice are capable of inducing Fas-mediated lysis of tumor target cells. In contrast, activated T cells from gld/gld mice fail to induce lysis of tumor targets, although cells from gld mice are able to lyse specific allogeneic targets following mixed lymphocyte culture. In addition, activated T cells from gld/gld homozygous animals are not capable of binding to a Fas.Fc fusion protein at high levels, whereas activated T cells from normal and lpr/lpr animals bind Fas.Fc efficiently. These data indicate that mice homozygous for gld are unable to express a functional ligand for Fas.
authors.affiliation: Department of Immunobiology, Immunex Research and Development Corporation, Seattle, WA 98101.
authors.forename: F
authors.initials: F
authors.lastname: Ramsdell
authors.forename: M S
authors.initials: MS
authors.lastname: Seaman
authors.forename: R E
authors.initials: RE
authors.lastname: Miller
authors.forename: T W
authors.initials: TW
authors.lastname: Tough
authors.forename: M R
authors.initials: MR
authors.lastname: Alderson
authors.forename: D H
authors.initials: DH
authors.lastname: Lynch
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics* / Q000502:physiology; D001327:Autoimmune Diseases / Q000235:genetics*; D003602:Cytotoxicity, Immunologic; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009154:Mutation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019014:fas Receptor
chemical_list: D000954:Antigens, Surface; D008024:Ligands; D019014:fas Receptor