Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetes
Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetes
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DOI：
10.1073/pnas.0708899104
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发表时间：
2007-11-13
影响因子：
11.1
通讯作者：
Benoist, Christophe
中科院分区：
文献类型：
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作者：
Feuerer, Markus;Jiang, Wenyu;Benoist, Christophe
FoxP3(+)CD4（+）调节性T细胞（treg）在维持外周自我耐受性中起关键作用，有研究表明，糖尿病易感非肥胖糖尿病（NOD）小鼠在treg的产生和数量上存在缺陷。我们发现treg的胸腺选择受遗传控制。NOD背景下的胎儿胸腺器官培养需要比B6背景下的相应培养多3- 10倍的抗原才能最佳诱导treg，但一旦达到诱导阈值，NOD背景下的treg产生接近10倍。这种增加的Tregs选择也发现在非转基因NOD小鼠从胎儿到成年阶段。该性状不映射到控制克隆缺失的MHC、idd3或3号染色体（Chr3）区域，而主要映射到Chr1和Chr11上的两个区域。因此，NOD小鼠在treg的产生或维持方面没有全局性缺陷；如果有什么不同的话，那就是相反。
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 non-transgenic 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.