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 (Th1)-dominant response as the dise ase progresses in non-obese diabetic (NOD) mice. However, the regulation of Th1/Th2 balance in spontaneous diabetes development in this model is not w ell 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 Th1-type response (IFN-gamma production) upon polyclonal (anti-CD3 antibody) stimulation was observed just before diabetes developm ent along with a decline of GAD65-specific IL-10 production. Moreover, ther e was a clear negative correlation between IL-10 level upon GAD65 stimulati on and log(IFN-gamma) level upon anti-CD3 antibody stimulation (r=0.999, p <0.001). These results suggest that the balance between GAD65-specific IL-10 product ion and polyclonal Th1-type response may regulate the onset of hyperglycemi a in type I diabetes in NOD mice.