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International Immunology Advance Access originally published online on September 24, 2009
International Immunology 2009 21(11):1291-1299; doi:10.1093/intimm/dxp097
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Critical role of IFN-{gamma} in CFA-mediated protection of NOD mice from diabetes development

Yoshiko Mori*, Tetsuro Kodaka*, Takako Kato, Edith M. Kanagawa and Osami Kanagawa

Laboratory for Autoimmune Regulation, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan

Correspondence to: O. Kanagawa; E-mail: kanagawa{at}rcai.riken.jp

IFN-{gamma} signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN-{gamma} signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN-{gamma} receptor-deficient (IFN-{gamma}R–/–) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN-{gamma} is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the Th1/Th17 balance between IFN-{gamma}R–/– NOD and wild-type NOD mice. There is also no difference in the total numbers and percentages of regulatory T (Treg) cells in the lymph node CD4+ T-cell populations between IFN-{gamma}R–/– NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-{gamma}R are resistant to the suppressive effect of Treg cells, both in vivo and in vitro. Therefore, it is likely that CFA-mediated protection against diabetes development depends on a change in the balance between Treg cells and pathogenic T cells, and IFN-{gamma} signaling seems to control the susceptibility of pathogenic T cells to the inhibitory activity of Treg cells.

Keywords: CFA, diabetes, IFN-{gamma}, NOD mice, regulatory T cells

* These authors contributed equally to this study.

Transmitting editor: H. Robson MacDonald

Received 21 March 2009, accepted 2 September 2009.


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