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.