Mechanism underlying counterregulation of autoimmune diabetes by IL-4

Immunity. 1997 Sep;7(3):411-8. doi: 10.1016/s1074-7613(00)80362-3.

Abstract

Diabetes in nonobese diabetic (NOD) mice is an autoimmune disease characterized by the destruction of the beta cells in the pancreas. We have previously reported that transgenic expression of interleukin-4 (IL-4) counterregulates the disease process, completely protecting NOD mice from insulitis and diabetes. Here we demonstrate the presence of autoreactivity but lack of pathogenicity of the IL-4-regulated lymphocytes. The importance of T cell diversity for the protective effect of IL-4 is demonstrated through breeding with transgenic BDC2.5 mice, which have an almost exclusively monoclonal T cell repertoire. Limitation of T cell diversity abrogated the protection by IL-4. We suggest that "immune deviation" in NOD-IL-4 mice is mediated by the pancreatic tissue itself, which causes activation of distinct, nonpathogenic T cell specificities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cyclophosphamide / toxicity
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control
  • Female
  • Immune Tolerance
  • Interleukin-4 / immunology*
  • Interleukin-4 / therapeutic use
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / immunology
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Receptors, Antigen, T-Cell
  • Interleukin-4
  • Cyclophosphamide