Mechanism underlying counterregulation of autoimmune diabetes by IL-4

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


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


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