Suppression of Th1 cell activation and prevention of autoimmune diabetes in NOD mice by local expression of viral IL-10

Shunsuke Kawamoto, Yoshio Nitta, Fumi Tashiro, Atsushi Nakano, Eiji Yamato, Hideaki Tahara, Koichi Tabayashi, Jun ichi Miyazaki

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30 Citations (Scopus)

Abstract

Insulin-dependent diabetes mellitus in the NOD mouse model is caused by the T cell-mediated autoimmune destruction of pancreatic β cells. Viral IL-10 (vIL-10), encoded in the Epstein-Barr 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-γ 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.

Original languageEnglish
Pages (from-to)685-694
Number of pages10
JournalInternational immunology
Volume13
Issue number5
DOIs
Publication statusPublished - 2001 Jan 1

Keywords

  • Autoimmunity
  • Cytokines
  • Diabetes
  • NOD mouse
  • Transgenic mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kawamoto, S., Nitta, Y., Tashiro, F., Nakano, A., Yamato, E., Tahara, H., Tabayashi, K., & Miyazaki, J. I. (2001). Suppression of Th1 cell activation and prevention of autoimmune diabetes in NOD mice by local expression of viral IL-10. International immunology, 13(5), 685-694. https://doi.org/10.1093/intimm/13.5.685