title: Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetes.
abstract: FoxP3(+)CD4(+) regulatory T cells (Tregs) play a key role in the maintenance of peripheral self-tolerance, and it has been suggested that diabetes-susceptible nonobese diabetic (NOD) mice are defective in the generation and numbers of Tregs. We found thymic selection of Tregs to be under genetic control. Fetal thymic organ cultures on the NOD background required 3- to 10-fold more antigen than corresponding cultures on the B6 background for optimal induction of Tregs, but once the threshold for induction was reached the NOD background yielded close to 10-fold more Tregs. This increased selection of Tregs was also found in nontransgenic NOD mice in fetal through adult stages. This trait did not map to the MHC, idd3, or the chromosome 3 (Chr3) regions that control clonal deletion, but mainly to two regions on Chr1 and Chr11. Thus, NOD mice do not have a global defect in the generation or maintenance of Tregs; if anything, they show the opposite.
authors.affiliation: Section on Immunology and Immunogenetics, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Feuerer
authors.forename: Wenyu
authors.initials: W
authors.lastname: Jiang
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Holler
authors.forename: Ansuman
authors.initials: A
authors.lastname: Satpathy
authors.forename: Christopher
authors.initials: C
authors.lastname: Campbell
authors.forename: Molly
authors.initials: M
authors.lastname: Bogue
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D009924:Organ Culture Techniques; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*