Development and function of diabetogenic T-cells in B-cell-deficient nonobese diabetic mice

Diabetes. 2001 Apr;50(4):763-70. doi: 10.2337/diabetes.50.4.763.

Abstract

Insulin-dependent diabetes (type 1 diabetes) in the NOD mouse is a T-cell-mediated autoimmune disease. However, B-cells may also play a critical role in disease pathogenesis, as genetically B-cell-deficient NOD mice (NOD.microMT) have been shown to be protected from type 1 diabetes and to display reduced responses to certain islet autoantigens. To examine the requirements for B-cells in the development of type 1 diabetes, we generated a B-cell-naive T-cell repertoire by transplantation of NOD fetal thymuses (FTs) into NOD.scid recipients. Surprisingly, these FT-derived NOD T-cells were diabetogenic in 36% of NOD.scid recipients, despite the absence of B-cells. In addition, T-cells isolated from NOD.microMT mice were diabetogenic in 22% of NOD.scid recipients. Together, these results indicate that B-cells are not an absolute requirement for the generation or effector function of an islet-reactive T-cell repertoire in NOD mice. We suggest that conditions favoring rapid lymphocyte expansion can reveal autoreactive T-cell activity and precipitate disease in genetically susceptible individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / pathology
  • B-Lymphocytes / physiology*
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Female
  • Fetal Tissue Transplantation
  • Male
  • Mice
  • Mice, Inbred NOD / anatomy & histology*
  • Mice, Inbred NOD / physiology*
  • Mice, SCID
  • Pancreas / pathology
  • T-Lymphocytes / physiology*