Enhanced thymic selection of FoxP3 + regulatory T cells in the NOD mouse model of autoimmune diabetes
| Autor: | Wenyu Jiang, Phillip D. Holler, Diane Mathis, Molly Bogue, Markus Feuerer, Ansuman T. Satpathy, Christopher L. Campbell, Christophe Benoist |
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| Rok vydání: | 2007 |
| Předmět: |
Fetus
Multidisciplinary FOXP3 hemic and immune systems chemical and pharmacologic phenomena Thymus Gland Nod Biological Sciences Biology Major histocompatibility complex T-Lymphocytes Regulatory Clonal deletion Mice Diabetes Mellitus Type 1 Organ Culture Techniques Species Specificity Chromosome 3 Antigen Mice Inbred NOD Immunology biology.protein Animals NOD mice |
| Zdroj: | Proceedings of the National Academy of Sciences. 104:18181-18186 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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