Following a diabetogenic T cell from genesis through pathogenesis

Cell. 1993 Sep 24;74(6):1089-100. doi: 10.1016/0092-8674(93)90730-e.

Abstract

Nonobese diabetic (NOD) mice spontaneously develop a disease very similar to type 1 diabetes in humans. We have generated a transgenic mouse strain carrying the rearranged T cell receptor genes from a diabetogenic T cell clone derived from a NOD mouse. Self-reactive T cells expressing the transgene-encoded specificity are not tolerized in these animals, resulting in rampant insulitis and eventually diabetes. Features of the disease process emphasize two so-called check-points, recognized previously in the NOD and human diseases but easily misinterpreted. Although NOD mice are protected from insulitis and diabetes by expression of the E molecule encoded in the major histocompatibility complex, the transgenics are not, permitting us to exclude some possible mechanisms of protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Flow Cytometry
  • Gene Rearrangement, T-Lymphocyte*
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Inbred NOD / immunology
  • Mice, Transgenic
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Pancreas / immunology
  • Pancreas / pathology
  • Polymerase Chain Reaction / methods
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Submandibular Gland / immunology
  • Submandibular Gland / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Oligodeoxyribonucleotides
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta