CD4+CD25+ regulatory T cells control the progression from periinsulitis to destructive insulitis in murine autoimmune diabetes

Cell Immunol. 2005 May;235(1):1-11. doi: 10.1016/j.cellimm.2005.05.003. Epub 2005 Aug 24.


Non-obese diabetic (NOD) mice develop spontaneous T-cell responses against pancreatic beta-cells, leading to islet cell destruction and diabetes. Despite high genetic similarity, non-obese resistant (NOR) mice do not develop diabetes. We show here that spleen cells of both NOD and NOR mice respond to the islet cell antigen glutamic acid decarboxylase-65 in IFN-gamma-ELISPOT assays. Moreover, NOR-T cells induce periinsulitis in NOD SCID recipient mice. Thus, a potentially pathogenic islet cell-specific T-cell response arises in NOR and NOD mice alike; the mechanism that prevents the autoimmune progression of self-reactive T cells in NOR mice presumably acts at the level of effector function. Consistent with this hypothesis, CD4+CD25+ cell-depleted spleen cells from NOR mice mediated islet cell destruction and overt diabetes in NOD SCID mice. Therefore, islet cell-specific effector cells in NOR mice appear to be under the control of CD4+CD25+ regulatory T cells, confirming the importance of regulatory cells in the control of autoimmune diabetes.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Diabetes Mellitus, Experimental / immunology*
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology*
  • Disease Progression
  • Female
  • Glutamate Decarboxylase / immunology
  • Homeodomain Proteins / genetics
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology*
  • Isoenzymes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Peptides / immunology
  • Receptors, Interleukin-2 / metabolism
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • Homeodomain Proteins
  • Isoenzymes
  • Peptides
  • Receptors, Interleukin-2
  • RAG-1 protein
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2