PRODUCTION OF INTERLEUKIN-10 BY ISLET CELLS ACCELERATES IMMUNE-MEDIATED DESTRUCTION OF BETA-CELLS IN NONOBESE DIABETIC MICE

The T helper type 2 (Th2) cell product interleukin 10 (IL-10) inhibits the proliferation and function of Th1 lymphocytes and macrophages (Mp hi). The nonobese diabetic mouse strain (NOD/Shi) develops a Mo and T cell-dependent autoimmune diabetes that closely resembles human insuli n-dependent diabetes mellitus (IDDM). The objective of the present stu dy was to explore the consequences of localized production of IL-10 on diabetes development in NOD/Shi mice. Surprisingly, local production of IL-10 accelerated the onset and increased the prevalence of diabete s, since diabetes developed at 5-10 wk of age in 92% of IL-10 positive I-Abeta(g7/g7), I-E- mice in first (N2) and second (N3) generation ba ckcrosses between IL-10 transgenic BALB/c mice and (NOD/Shi) mice. Non e of the IL-10 negative major histocompatibility complex-identical lit termates were diabetic at this age. Furthermore, diabetes developed in 33% of I-Abeta(g7/d), I-E+ N3 mice in the presence of IL-10 before th e mice were 10 wk old. Our findings support the notion that IL-10 shou ld not simply be regarded as an immunoinhibitory cytokine, since it po ssesses powerful, immunostimulatory properties as well. Furthermore, o ur observations suggest that beta cell destruction in NOD mice may be a Th2-mediated event.