GENETIC REQUIREMENTS FOR ACCELERATION OF DIABETES IN NONOBESE DIABETIC MICE EXPRESSING INTERLEUKIN-2 IN ISLET BETA-CELLS

Diabetes was dramatically accelerated in non-obese diabetic (NOD) tran sgenic mice that expressed interleukin-2 (IL-2) in their beta cells. A single cross to C57BL/6 completely prevented this effect and a furthe r backcross to the NOD genetic background showed that at least two dia betes susceptibility loci (Idd1s and Idd3/10s) were required for the d iabetes acceleration. T cells activated to islet antigens were not cir culating in the mice. The accelerating effect of IL-2 was present, but decreased, in NOD mice that lacked CD8(+) T cells as well as in NOD S CID mice. The implications are that in the NOD genetic background, the production of cytokines, such as IL-2, by islet-specific CD4(+) T cel ls can lead to beta cell damage and diabetes and that CD8(+) T cells m ay have a role in accelerating diabetes onset.