The role of interferon-gamma in autoimmune diabetes was assessed by breeding a null mutation of the interferon-gamma receptor of 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.
Xavier Fredy René Quaglia-Thermes, Giacomo Olimpio Diaceri, Jeffrey Alan Hubbell, Sachiko Hirosue, David Scott Wilson, Martina Damo, Michal Mateusz Raczy
Michele De Palma, Davide Demurtas, Romain Hamelin, Jeffrey Alan Hubbell, Melody Swartz, Steinunn Baekkeskov Hanahan, Sachiko Hirosue, Chiara Cianciaruso, Miriella Carmela Pasquier, Edward Allen Phelps