title: Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes.
abstract: The role of interferon-gamma in autoimmune diabetes was assessed by breeding a null mutation of the interferon-gamma receptor alpha chain into the nonobese diabetic mouse strain, as well as into a simplified T cell receptor transgenic model of diabetes. In contrast to a previous report on abrogation of the interferon-gamma gene, mutation of the gene encoding its receptor led to drastic effects on disease in both mouse lines. Nonobese diabetic mice showed a marked inhibition of insulitis-both the kinetics and penetrance-and no signs of diabetes; the transgenic model exhibited near-normal insulitis, but this never evolved into diabetes, either spontaneously or after experimental provocation. This failure could not be explained by perturbations in the ratio of T helper cell phenotypes; rather, it reflected a defect in antigen-presenting cells or in the islet beta cell targets.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (Centre National de la Recherche Scientifique/Institut National de la Sant-e et de la Recherche M-edicale/Universit-e Louis Pasteur) 1, 67404 Illkirch, C.U. de Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: I
authors.initials: I
authors.lastname: André
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez
authors.forename: J D
authors.initials: JD
authors.lastname: Katz
authors.forename: M
authors.initials: M
authors.lastname: Aguet
authors.forename: C
authors.initials: C
authors.lastname: Benoist
authors.forename: D
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000502:physiology*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology; D017471:Receptors, Interferon / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor