Differential Regulatory Function of Resting and Preactivated Allergen-Specific CD4+CD25+ Regulatory T Cells in Th2-Type Airway Inflammation
Differential Regulatory Function of Resting and Preactivated Allergen-Specific CD4+CD25+ Regulatory T Cells in Th2-Type Airway Inflammation
复制标题
DOI：
10.4049/jimmunol.181.10.6889
复制
发表时间：
2008-11-15
影响因子：
4.4
通讯作者：
Kato, Takuma
中科院分区：
文献类型：
--
作者：
Saito, Kanako;Torii, Mie;Kato, Takuma
虽然CD4(+)CD25（+）调节性T （Treg）细胞已知可抑制Th1细胞介导的免疫反应，但其对th2型免疫反应的影响尚不清楚。在这项研究中，我们研究了Treg细胞在小鼠th2型气道炎症中的作用。耗尽和重建实验表明，幼稚小鼠的Treg细胞有效抑制th2驱动的气道炎症的发生和发展。尽管在幼稚小鼠中th2型气道炎症得到了有效的抑制，但过继转移后，过敏原特异性Treg细胞无法抑制过敏原致敏小鼠的气道炎症。然而，预先激活的过敏原特异性Treg细胞可以通过在肺部积聚来抑制气道炎症，从而减少Th2细胞的积聚和增殖，即使在过敏原存在的小鼠中也是如此。激活后，过敏原特异性Treg细胞上调CCR4，对CCR4配体表现出增强的趋化反应，并抑制极化Th2细胞的增殖和细胞因子的产生。总的来说，这些结果表明Treg细胞能够抑制Th2驱动的气道炎症，甚至在过敏原存在的小鼠中，其方式依赖于它们有效迁移到炎症部位并调节Th2细胞的激活和增殖。免疫学杂志，2008,18(1):689 - 697。
Although CD4(+)CD25(+) regulatory T (Treg) cells are known to suppress Th1 cell-mediated immune responses, their effect on Th2-type immune responses remains unclear. In this study we examined the role of Treg cells in Th2-type airway inflammation in mice. Depletion and reconstitution experiments demonstrated that the Treg cells of naive mice effectively suppressed the initiation and development of Th2-driven airway inflammation. Despite effective suppression of Th2-type airway inflammation in naive mice, adoptively transferred, allergen-specific Treg cells were unable to suppress airway inflammation in allergen-presensitized mice. Preactivated allergen-specific Treg cells, however, could suppress airway inflammation even in allergen-presensitized mice by accumulating in the lung, where they reduced the accumulation and proliferation of Th2 cells. Upon activation, allergen-specific Treg cells up-regulated CCR4, exhibited enhanced chemotactic responses to CCR4 ligands, and suppressed the proliferation of and cytokine production by polarized Th2 cells. Collectively, these results demonstrated that Treg cells are capable of suppressing Th2-driven airway inflammation even in allergen-presensitized mice in a manner dependent on their efficient migration into the inflammatory site and their regulation of Th2 cell activation and proliferation. The Journal of Immunology, 2008, 181: 6889-6897.