Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin
Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin
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DOI：
10.4049/jimmunol.180.9.5794
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Riley, James L.
中科院分区：
文献类型：
--
作者：
Basu, Samik;Golovina, Tatiana;Riley, James L.
在体外扩增的自然IF细胞中加入雷帕霉素有助于维持其抑制活性，但其机制尚不清楚。PIM2是一种丝氨酸/苏氨酸激酶，可诱导雷帕霉素耐药。在新鲜分离的静息T细胞中，Pim 2呈结构性表达，而在经雷帕霉素诱导的Pim 2表达和优先扩增的CD4+CD2 5(-)T细胞中不表达，提示Foxp3可调节Pim 2的表达。最后，我们确定在雷帕霉素存在的情况下，Treg的扩展与Toxp3的表达呈正相关。总之，这些结果表明Tregs被编程为对雷帕霉素具有耐药性，这为为什么这种免疫抑制药物应该与扩大的Tregs联合使用提供了进一步的理由。
Addition of rapamycin to cultures of expanding natural If CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) helps maintain their suppressive activity, but the underlying mechanism is unclear. Pim 2 is a serine/threonine kinase that can confer rapamycin resistance. Unexectedly, pim 2 was found to be constitutively expressed in freshly isolated, resting Tregs, but not in CD4(+) CD25(-) T effector T cells induced pim 2 expression and conferred preferential expansion in the presence of rapamycin, indicating that Foxp3 can regulate pim 2 expression. Finally, we determined there is a positive correlation between Treg expansion and Toxp3 expression in the presence of rapamycin. Together, these results indicate that Tregs are programmed to be resistant to rapamycin, providing further rationale for why this immunosuppressive drug should be used in conjunction with expanded Tregs.