Balance of GAD65-specific IL-10 production and polyclonal Th1-type response in type 1 diabetes.

It has been proposed that cytokine responses of memory CD4+ cells change from a T-helper 2 (Th2)-to a T-helper 1 (Thl)-dominant response as the disease progresses in non-obese diabetic (NOD) mice. However, the regulation of Thl/Th2 balance in spontaneous diabetes development in this model is not well understood. In this study, higher glutamic acid decarboxylase 65 (GAD65)-specific IL-10 production was observed at 10-12 weeks in NOD mice, and a marked increase of Thl-type response (IFN-γ production) upon polyclonal (anti-CD3 antibody) stimulation was observed just before diabetes development along with a decline of GAD65-specific IL-10 production. Moreover, there was a clear negative correlation between IL-10 level upon GAD65 stimulation and log(IFN-γ) level upon anti-CD3 antibody stimulation (r==0.999, p<0.001).These results suggest that the balance between GAD65-specific IL-10 production and polyclonal Thl-type response may regulate the onset of hyperglycemia in type 1 diabetes in NOD mice