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 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.
Univ Strasbourg 1,Cnrs,Inserm,Inst Genet & Biol Mol & Cellulaire,F-67404 Illkirch Graffens,France Ludwig Inst Canc Res,Ch-1066 Epalinges,Switzerland
Record created on 2007-12-12, modified on 2016-08-08