Nitta Y, Kawamoto S, Tashiro F, Aihara H, Yoshimoto T, Nariuchi H, Tabayashi K, Miyazaki J
Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
J Autoimmun. 2001 Mar;16(2):97-104. doi: 10.1006/jaut.2000.0469.
Accumulating evidence suggests that CD4(+)T helper type 1 (Th1) cells play a major role in the development of insulin-dependent diabetes mellitus (IDDM) in the non-obese diabetic (NOD) mouse model. Interleukin (IL)-12 is a potent immunoregulatory molecule that is a key determinant of T-cell differentiation into Th1 cells, and has been implicated in the development of IDDM. To investigate the role of IL-12 that is locally produced by islet-infiltrating cells in the development of IDDM, we generated transgenic NOD mice in which the IL-12 p40 homodimer, a natural antagonist of IL-12, was produced exclusively in islets without affecting the levels of IL-12 p40 in the systemic circulation. We found that the incidence of diabetes was significantly reduced in these transgenic mice. These results clearly demonstrate that IL-12 locally produced by islet-infiltrating cells plays a critical role in the development of IDDM.
