Cutting edge: type 1 diabetes occurs despite robust anergy among endogenous insulin-specific CD4 T cells in NOD mice

J Immunol. 2013 Nov 15;191(10):4913-7. doi: 10.4049/jimmunol.1301927. Epub 2013 Oct 11.

Abstract

Insulin-specific CD4(+) T cells are required for type 1 diabetes. How these cells are regulated and how tolerance breaks down are poorly understood because of a lack of reagents. Therefore, we used an enrichment method and tetramer reagents to track insulin-specific CD4(+) T cells in diabetes-susceptible NOD and resistant B6 mice expressing I-A(g7). Insulin-specific cells were detected in both strains, but they only became activated, produced IFN-γ, and infiltrated the pancreas in NOD mice. Unexpectedly, the majority of Ag-experienced cells in NOD mice displayed an anergic phenotype, but this population decreased with age as tolerance was lost. B6 mice expressing I-A(g7) were protected because insulin-specific cells did not become effector or anergic T cells but remained naive. These data suggest that NOD mice promote tolerance through anergy induction, but a small proportion of autoreactive T cells escape anergy to provoke type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Clonal Anergy / immunology*
  • Diabetes Mellitus, Experimental / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Insulin / immunology
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred NOD
  • Pancreas / cytology
  • Pancreas / immunology

Substances

  • Insulin
  • Interferon-gamma