Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice

Genes Immun. 2014 Mar;15(2):82-7. doi: 10.1038/gene.2013.65. Epub 2014 Jan 16.

Abstract

Immunoregulatory T cells have been identified as key modulators of peripheral tolerance and participate in preventing autoimmune diseases. CD4(-)CD8(-) (double negative, DN) T cells compose one of these immunoregulatory T-cell subsets, where the injection of DN T cells confers protection from autoimmune diabetes progression. Interestingly, genetic loci defining the function and number of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) coincide with at least some autoimmune disease susceptibility loci. Herein, we investigate the impact of major insulin-dependent diabetes (Idd) loci in defining the number of DN T cells. We demonstrate that although Idd3, Idd5 and Idd9 loci do not regulate DN T-cell number, NOD mice congenic for diabetes resistance alleles at the Idd13 locus show a partial restoration in DN T-cell number. Moreover, competitive and non-competitive bone marrow chimera experiments reveal that DN T-cell number is defined by a bone marrow-intrinsic, but DN T-cell-extrinsic, factor. This suggests that non-autonomous candidate genes define DN T-cell number in secondary lymphoid organs. Together, our results show that the regulation of DN T-cell number in NOD mice is at least partially conferred by alleles at the Idd13 locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / genetics
  • CD8 Antigens / genetics
  • Diabetes Mellitus, Type 1 / genetics*
  • Genetic Predisposition to Disease
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Peripheral Tolerance / genetics
  • Peripheral Tolerance / immunology*
  • T-Lymphocyte Subsets / immunology*

Substances

  • CD4 Antigens
  • CD8 Antigens

Supplementary concepts

  • Diabetes Mellitus, Insulin-Dependent, 13
  • Diabetes Mellitus, Insulin-Dependent, 5