Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential

J Exp Med. 1993 Mar 1;177(3):627-36. doi: 10.1084/jem.177.3.627.


Diabetes was induced in a normal nonautoimmune rat strain by rendering the animals relatively T cell deficient using a protocol of adult thymectomy and sublethal gamma irradiation. All male rats and 70% of females developed an acute syndrome with severe loss of weight and hyperglycemia. Diabetes in these lymphopoenic rats was associated with extensive insulitis involving CD4+ and CD8+ T cells and macrophages. The CD8+ T cells were essential for the development of diabetes but not insulitis. The autoimmune diabetes and insulitis were completely prevented by the injection of a particular CD4+ T cell subset, isolated from healthy syngeneic donors, of the phenotype CD45RClow T cell receptor alpha/beta+ RT6+ Thy-1- OX-40-. Cells of this protective phenotype, which make up about 5% of thoracic duct lymphocytes, were found to provide help for secondary antibody responses and produce interleukin 2 (IL-2) and IL-4, but no interferon gamma, on in vitro activation. These data provide evidence for the presence of autoreactive T cells in the normal immune system of the rat and reveal that in the intact animal these cells are prevented from expressing their autoreactive potential by other T cells.

MeSH terms

  • Animals
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmunity / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8 Antigens / analysis
  • Diabetes Mellitus, Experimental / etiology*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Female
  • Flow Cytometry
  • Immunohistochemistry
  • Interleukin-10 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Leukocyte Common Antigens / analysis
  • Lymphocyte Depletion
  • Macrophages / immunology
  • Macrophages / pathology
  • Male
  • Phenotype
  • Rats
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocyte Subsets / physiology*
  • Thymectomy


  • CD8 Antigens
  • Interleukin-2
  • Receptors, Antigen, T-Cell, alpha-beta
  • Interleukin-10
  • Interleukin-4
  • Leukocyte Common Antigens