Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes.
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.
Wang
B
B
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.
André
I
I
Gonzalez
A
A
Katz
J D
JD
Aguet
M
M
Benoist
C
C
Mathis
D
D
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
D007371:Interferon-gamma; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor