title: Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility.
abstract: Regulatory T (Treg) lymphocytes play a central role in the control of autoimmune pathology. Any alteration in Treg-cell biology in mouse strains used for the study of these disorders therefore raises the question of its direct link with disease susceptibility. Paradoxically, in non-obese diabetic (NOD) mice increased numbers of Treg cells develop in the thymus. In this report we identify a locus of <7 Mbp that quantitatively controls Treg-cell development in the thymus of the NOD mouse. This 'Trd1' region is located centromeric to the H2 complex on chromosome 17 and does not include genes encoding classical MHC molecules. The genomic region identified here contains the Idd16 diabetes susceptibility locus and the use of congenic mouse strains allowed us to investigate the potential link between quantitatively altered thymic Treg cells and diabetes susceptibility. Hybrid mice present similar levels of thymic Treg cells as B6 animals but they developed diabetes with the same kinetics as NOD mice. Therefore, the increased Treg-cell development in NOD mice controlled by Trd1 is functionally dissociated from the susceptibility of NOD to diabetes.
authors: Inserm, U1043, Toulouse, France.
authors: Julie
authors: J
authors: Tellier
authors: Andry
authors: A
authors: Andrianjaka
authors: Rita
authors: R
authors: Vicente
authors: Nicolas
authors: N
authors: Thiault
authors: Geneviève
authors: G
authors: Enault
authors: Henri-Jean
authors: HJ
authors: Garchon
authors: Joost P M
authors: JP
authors: van Meerwijk
authors: Paola
authors: P
authors: Romagnoli
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D003920:Diabetes Mellitus / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology*