The T helper type 2 (Th2) cell product interleukin 10 (IL-10) inhibits the proliferation and function of Thl lymphocytes and macrophages (Mø) The nonobese diabetic mouse strain (NOD/Shi) develops a Me and T cell-dependent autoimmune diabetes that closely resembles human insulindependent diabetes mellitus (IDDM). The objective of the present study 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 diabetes, since diabetes developed at 5-10 wk of age in 92% of IL-IO positive I-A/³g 7/g7, I-E- mice in first (N2) and second (N3) generation backcrosses between IL-10 transgenic BALB/c mice and (NOD/Shi) mice. None of the IL-10 negative major histocompatibility complex-identical littermates were diabetic at this age. Furthermore, diabetes developed in 33% of I-A/³g TM, I-E + N3 mice in the presence of IL-10 before the mice were 10 wk old. Our findings support the notion that IL-10 should not simply be regarded as an immunoinhibitory cytokine, since it possesses powerful, immunostimulatory properties as well. Furthermore, our observations suggest that/3 cell destruction in NOD mice may be a Th2-mediated event.
ASJC Scopus subject areas
- Immunology and Allergy