CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells.
CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells.
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DOI：
10.1084/jem.20061405
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发表时间：
2007-04-16
影响因子：
15.3
通讯作者：
Rot, Antal
中科院分区：
文献类型：
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作者：
Schneider, Martin A;Meingassner, Josef G;Lipp, Martin;Moore, Henrietta D;Rot, Antal
CCR7介导的幼稚T细胞向次级淋巴器官的迁移是它们与成熟树突状细胞相遇、同源抗原的生产性呈递以及随后的T细胞增殖和效应分化的先决条件。因此，CCR7被认为在适应性免疫应答的启动中起重要作用。在这项研究中，我们表明，原发性免疫也可以在没有CCR 7的情况下发展。此外，CCR7缺陷敲除（KO）小鼠显示增强的免疫应答。我们的数据累积表明，CCR7 KO小鼠的免疫增强是由FoxP3+ CD4+ CD25+调节性T细胞（T reg细胞）的淋巴结（LN）定位缺陷及其功能障碍引起的。FoxP3+ T reg细胞表达CCR7，并且在其过继转移后，迁移到野生型小鼠的LN中。在这里，它们在抗原刺激后原位增殖并抑制抗原特异性T细胞的产生。相反，转移的CCR7缺陷型T reg细胞不能迁移到LN中并抑制抗原诱导的T细胞应答。将来自野生型和CCR7 KO小鼠的初始和T reg细胞的组合转移到同系严重联合免疫缺陷小鼠中直接证明了CCR7缺陷型T reg细胞在预防炎性肠病发展方面不如其野生型对应物有效。
CCR7-mediated migration of naive T cells into the secondary lymphoid organs is a prerequisite for their encounter with mature dendritic cells, the productive presentation of cognate antigen, and consequent T cell proliferation and effector differentiation. Therefore, CCR7 was suggested to play an important role in the initiation of adaptive immune responses. In this study, we show that primary immunity can also develop in the absence of CCR7. Moreover, CCR7-deficient knockout (KO) mice display augmented immune responses. Our data cumulatively suggest that enhanced immunity in CCR7 KO mice is caused by the defective lymph node (LN) positioning of FoxP3+ CD4+ CD25+ regulatory T cells (T reg cells) and the consequent impediment of their function. The FoxP3+ T reg cells express CCR7 and, after their adoptive transfer, migrate into the LNs of wild-type mice. Here, they proliferate in situ upon antigen stimulation and inhibit the generation of antigen-specific T cells. Conversely, transferred CCR7-deficient T reg cells fail to migrate into the LNs and suppress antigen-induced T cell responses. The transfer of combinations of naive and T reg cells from wild-type and CCR7 KO mice into syngeneic severe combined immunodeficient mice directly demonstrates that CCR7-deficient T reg cells are less effective than their wild-type counterparts in preventing the development of inflammatory bowel disease.