Regulatory T cells prevent transfer of type 1 diabetes in NOD mice only when their antigen is present in vivo

J Immunol. 2008 Oct 1;181(7):4516-22. doi: 10.4049/jimmunol.181.7.4516.


Regulatory T cells (Tregs) can potentially be used as tools to suppress pathogenic T cells in autoimmune diseases such as type 1 diabetes. For use in therapy it is critically important to determine whether suppression by Tregs requires a population specific for the target of autoimmunity, such as pancreatic beta cells in type 1 diabetes. Current reports in the NOD mouse model of type 1 diabetes are in conflict as to whether suppression of disease by Tregs is Ag-dependent. We have addressed this question by evaluating the effects of islet-specific TGF-beta-induced Tregs in recipient mice in which the Treg Ag is either present or absent. Our data show that Treg numbers in pancreas are reduced in the absence of Ag and that there are Ag-dependent differences in the effects of Tregs on pathogenic T cells in the pancreas. By examining protection from diabetes induced by T cell transfer, we have clearly demonstrated that Tregs suppress only in the presence of their Ag and not in mice in which the islets lack the Treg Ag. Our results also suggest that in sufficiently large populations of polyclonal Tregs, there will be adequate numbers of islet-specific Tregs to suppress diabetes.

Publication types

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

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Clone Cells
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Epitopes, T-Lymphocyte / biosynthesis
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / physiology*
  • Immunosuppression Therapy
  • Islets of Langerhans / immunology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / biosynthesis
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / deficiency
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / transplantation*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism


  • Cytokines
  • Epitopes, T-Lymphocyte
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8