title: Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice.
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.
authors: 1] Research Center, Immunology-Oncology Section, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada [2] Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
authors: V
authors: V
authors: Dugas
authors: Autoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and University of Leuven, Leuven, Belgium.
authors: A
authors: A
authors: Liston
authors: 1] Research Center, Immunology-Oncology Section, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada [2] Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
authors: E E
authors: EE
authors: Hillhouse
authors: 1] Research Center, Immunology-Oncology Section, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada [2] Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
authors: R
authors: R
authors: Collin
authors: Research Center, Immunology-Oncology Section, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada.
authors: G
authors: G
authors: Chabot-Roy
authors: 1] Research Center, Immunology-Oncology Section, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada [2] Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
authors: A-N
authors: AN
authors: Pelletier
authors: 1] Research Center, Immunology-Oncology Section, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada [2] Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
authors: C
authors: C
authors: Beauchamp
authors: Division of Biomedical Sciences, University of Canberra, Bruce, Canberra, Australia.
authors: K
authors: K
authors: Hardy
authors: 1] Research Center, Immunology-Oncology Section, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada [2] Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
authors: S
authors: S
authors: Lesage
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D061166:Peripheral Tolerance / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens