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

Int Immunol. 2009 Nov;21(11):1291-9. doi: 10.1093/intimm/dxp097. Epub 2009 Sep 24.

Abstract

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-gammaR(-/-)) 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 T(h)1/T(h)17 balance between IFN-gammaR(-/-) 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-gammaR(-/-) NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-gammaR 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.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Freund's Adjuvant / therapeutic use*
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology*
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Receptors, Interferon / genetics
  • Receptors, Interferon / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Adjuvants, Immunologic
  • Receptors, Interferon
  • interferon gamma receptor
  • Interferon-gamma
  • Freund's Adjuvant