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

研究成果: Article査読

30 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)685-694
ページ数10
ジャーナルInternational immunology
13
5
DOI
出版ステータスPublished - 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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