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

V. Dugas, A. Liston, E. E. Hillhouse, R. Collin, G. Chabot-Roy, A. N. Pelletier, C. Beauchamp, Kris HARDY, S. Lesage

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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.

Original languageEnglish
Pages (from-to)82-87
Number of pages6
JournalGenes and Immunity
Volume15
Issue number2
DOIs
Publication statusPublished - 2014

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Dugas, V., Liston, A., Hillhouse, E. E., Collin, R., Chabot-Roy, G., Pelletier, A. N., ... Lesage, S. (2014). Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice. Genes and Immunity, 15(2), 82-87. https://doi.org/10.1038/gene.2013.65