Peripheral T cell lymphopenia and concomitant enrichment in naturally arising regulatory T cells:: The case of the pre-Tα gene-deleted mouse

Peripheral T cell lymphopenia and concomitant enrichment in naturally arising regulatory T cells:: The case of the pre-Tα gene-deleted mouse
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DOI:
10.4049/jimmunol.177.8.5014
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发表时间:
2006-10-15
影响因子:
4.4
通讯作者:
Ceredig, Rhodri
Ceredig, Rhodri
中科院分区:
医学2区
文献类型:
--
作者:
Bosco, Nabil;Agenes, Fabien;Ceredig, Rhodri

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在前Tα(pTα)基因缺失小鼠中,阳性选择性CD4(+)CD8(+)双阳性胸腺细胞池仅为野生型小鼠的1%。因此,它们的外周T细胞室严重淋巴细胞减少,同时CD25(+)FOXP3(+)调节性T细胞比例增加。使用混合骨髓。在嵌合体中,胸腺输出为正常值的 1%,pT α(-/-) 外周 T 细胞表型可以用正常细胞复制。在pT α(-/-)胸腺和外周淋巴器官中,FoxP3(+)CD4(+)细胞富集。联体共生实验表明,许多pT α(-/-)CD4(+)单阳性胸腺细胞代表再循环外周T细胞。因此,FoxP3+CD4+单阳性胸腺细胞的富集不仅仅归因于胸腺产生的增加。因此,pT alpha(-/-) 小鼠作为模型系统,用于研究胸腺 T 细胞产生长期减少对外周 T 细胞区室生理学的影响。
In pre-T alpha (pT alpha) gene-deleted mice, the positively selectable CD4(+)CD8(+) double-positive thymocyte pool is only 1% that in wild-type mice. Consequently, their peripheral T cell compartment is severely lymphopenic with a concomitant increase in proportion of CD25(+)FOXP3(+) regulatory T cells. Using mixed bone marrow. chimeras, where thymic output was 1% normal, the pT alpha(-/-) peripheral T cell phenotype could be reproduced with normal cells. In the pT alpha(-/-) thymus and peripheral lymphoid organs, FoxP3(+)CD4(+) cells were enriched. Parabiosis experiments showed that many pT alpha(-/-)CD4(+) single-positive thymocytes represented recirculating peripheral T cells. Therefore, the enrichment of FoxP3+CD4+ single-positive thymocytes was not solely due to increased thymic production. Thus, the pT alpha(-/-) mouse serves as a model system with which to study the consequences of chronic decreased thymic T cell production on the physiology of the peripheral T cell compartment.