J. Allison et al., GENETIC REQUIREMENTS FOR ACCELERATION OF DIABETES IN NONOBESE DIABETIC MICE EXPRESSING INTERLEUKIN-2 IN ISLET BETA-CELLS, European Journal of Immunology, 24(10), 1994, pp. 2535-2541
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.