Migration matters:: regulatory T-cell compartmentalization determines suppressive activity in vivo
Migration matters:: regulatory T-cell compartmentalization determines suppressive activity in vivo
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DOI：
10.1182/blood-2005-05-1864
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发表时间：
2005-11-01
期刊：
影响因子：
20.3
通讯作者：
Huehn, J
中科院分区：
文献类型：
--
作者：
Siegmund, K;Feuerer, M;Huehn, J
调节性 T 细胞 (Treg) 在抑制不同免疫反应中发挥着重要作用；然而，它们在体内发挥抑制功能的区室尚不清楚。尽管许多研究小组已经描述了炎症部位内存在Tregs，但尚未证明发炎组织确实是主动抑制正在进行的免疫反应的部位。在这里，通过使用来自岩藻糖基转移酶 VII 缺陷动物的 α(+)(E) 效应/记忆样 Tregs（缺乏 E/P-选择素配体并且无法迁移到发炎部位），我们分析了适当的 Treg 定位对于炎症模型中体内抑制能力的功能重要性。缺乏 E/P-选择素配体的 Tregs 缺乏抑制表明，迁移到发炎部位是体内炎症反应消退的先决条件，因为这些选择素配体仅调节进入发炎组织。相比之下，与寻求炎症的对应物相比，幼稚样α(-)(E)CD25(+) Treg亚群优先通过淋巴结再循环，可以更有效地控制免疫反应诱导阶段幼稚CD4(+) T细胞的增殖。总之，这些发现提供了第一个确凿的证据，证明适当的定位对于 Tregs 的体内活性至关重要，并且可能对针对招募机制的抗炎治疗具有重要意义。
Regulatory T cells (Tregs) play a fundamental role in the suppression of different immune responses; however, compartments at which they exert suppressive functions in vivo are unknown. Although many groups have described the presence of Tregs within inflammatory sites, it has not been shown that inflamed tissues are, indeed, the sites of active suppression of ongoing immune reactions. Here, by using alpha(+)(E) effector/memory-like Tregs from fucosyltransferase VII-deficient animals, which lack E/P-selectin ligands and fail to migrate into inflamed sites, we analyzed the functional importance of appropriate Treg localization for in vivo suppressive capacity in an inflammation model. Lack of suppression by Tregs deficient in E/P-selectin ligands demonstrates that immigration into inflamed sites is a prerequisite for the resolution of inflammatory reactions in vivo because these selectin ligands merely regulate entry into inflamed tissues. In contrast, control of proliferation of naive CD4(+) T cells during the induction phase of the immune response is more efficiently exerted by the naive-like alpha(-)(E)CD25(+) Treg subset preferentially recirculating through lymph nodes when compared with its inflammation-seeking counterpart. Together, these findings provide the first conclusive evidence that appropriate localization is crucial for in vivo activity of Tregs and might have significant implications for anti-inflammatory therapies targeting recruitment mechanisms.