Plasticity of regulatory T cells: Subversion of suppressive function and conversion to enhancement of lung allergic responses
Plasticity of regulatory T cells: Subversion of suppressive function and conversion to enhancement of lung allergic responses
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DOI：
10.4049/jimmunol.180.11.7117
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Gelfand, Erwin W.
中科院分区：
文献类型：
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作者：
Joetham, Anthony;Matsubara, Shigeki;Gelfand, Erwin W.
CD4(+)CD25(+)Foxp3(+)天然存在的调节性T细胞(nTregs)的激活导致肺部过敏反应的抑制，这需要nTregs和CD8上的MHC I类相互作用。在缺乏 CD8（CD8(-/-) 受体）的情况下，转移的 nTreg 恢复了过敏原暴露后的气道高反应性、嗜酸性粒细胞炎症和 IL-13 水平。肺部过敏反应的增强伴随着转移的 nTreg 中 Foxp3 表达的减少和 IL-13 表达的增加。在用糖皮质激素诱导的TNFR相关蛋白配体抗体预处理的CD8(-/-)受体中，转移的nTregs维持高水平的Foxp3并且不会导致肺部反应改变。因此，可以通过降低Foxp3的表达来破坏nTregs的调节功能，并通过糖皮质激素诱导的TNFR相关蛋白的信号传导将nTregs转化为产生IL-13的CD4+T细胞，介导肺部过敏反应。
Activation of CD4(+)CD25(+)Foxp3(+) naturally occurring regulatory T cells (nTregs) resulting in suppression of lung allergic responses requires interaction of MHC class I on nTregs and CD8. In the absence of CD8 (CD8(-/-) recipients), transferred nTregs restored airway hyperresponsiveness, eosinophilic inflammation, and IL-13 levels following allergen exposure. Enhancement of lung allergic responses was accompanied by reduced expression of Foxp3 and increased expression of IL-13 in the transferred nTregs. In CD8(-/-) recipients pretreated with glucocorticoid-induced TNFR-related protein-ligand Ab, the transferred nTregs maintained high levels of Foxp3 and did not result in altered lung responses. Thus, the regulatory function of nTregs can be subverted by reducing the expression of Foxp3 and following signaling through glucocorticoid-induced TNFR-related protein are converted nTregs into IL-13-producing CD4(+) T cells mediating lung allergic responses.