International Immunology, Vol. 13, No. 5, 685-694,
May 2001
© 2001 Japanese Society for Immunology
Suppression of Th1 cell activation and prevention of autoimmune diabetes in NOD mice by local expression of viral IL-10
Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Suita, Osaka 565-0871, Japan
Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan
Department of Surgery, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Correspondence to: J.-i. Miyazaki
Insulin-dependent diabetes mellitus in the NOD mouse model is caused by the T cell-mediated autoimmune destruction of pancreatic ß cells. Viral IL-10 (vIL-10), encoded in the EpsteinBarr virus genome, shares many of the anti-inflammatory properties of cellular IL-10, but lacks its immunostimulatory properties. In the present study, we generated transgenic (Tg) NOD mice in which vIL-10 was produced exclusively in pancreatic islets and investigated the effect of vIL-10 on the development of diabetes. The accumulation of lymphocytes around islets was more prominent, but the invasive insulitis decreased in the vIL-10 Tg mice. The incidence of diabetes was markedly reduced in the vIL-10 Tg mice, in clear contrast to the accelerated diabetes seen in the murine IL-10 Tg NOD mice. IL-12p40 and IFN-
mRNA levels were decreased in pancreata of the vIL-10 Tg mice, although CD4 mRNA level was markedly increased. These results suggest that locally produced vIL-10 induced leukocyte migration, but inhibited the activation of Th1, probably through suppressing the production of IL-12. They indicate that vIL-10 may well be superior to cellular IL-10 in the treatment of autoimmune diabetes. The vIL-10 Tg NOD mice should provide a useful tool for understanding the differential action of vIL-10 versus cellular IL-10.
Keywords: autoimmunity, cytokines, diabetes, NOD mouse, transgenic mouse
Transmitting editor: S.-i. Nishikawa
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