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 language | English |
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Pages (from-to) | 82-87 |
Number of pages | 6 |
Journal | Genes and Immunity |
Volume | 15 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2014 |