GENETIC ABSENCE OF GAMMA-INTERFERON DELAYS BUT DOES NOT PREVENT DIABETES IN NOD MICE

Cytokines, particularly interferons, may participate in the developmen t of type I diabetes, This involvement could be from direct cytotoxic actions of the interferons on the pancreatic beta-cells or from an ind irect influence on the number, activity, or type of inflammatory cells that invade the islets in type I diabetes, To examine directly the ro le of interferon (IFN)-gamma in a mouse model of type I diabetes, we h ave introduced an inactivating mutation in the IFN-gamma gene (ifg) in to NOD mice. The genetic absence of IFN-gamma does not prevent either insulitis or diabetes in the NOD mice, but it does increase the time t o onset; Although it might have been predicted that the absence of IFN -gamma in these mice would lead to an increase in expression of Th2 T- helper cell-related cytokines, we found instead a profound decrease in the expression of two of the characteristic Th2 cytokines, interleuki n (IL)-4 and IL-10. We also demonstrate that the splenocytes taken fro m IFN-gamma-deficient diabetic mice are fully capable of transferring diabetes to naive recipients.