Rules of chemokine receptor association with T cell polarization in vivo
Rules of chemokine receptor association with T cell polarization in vivo
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DOI：
10.1172/jci13543
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发表时间：
2001-11-01
影响因子：
15.9
通讯作者：
Butcher, EC
中科院分区：
文献类型：
--
作者：
Kim, CH;Rott, L;Butcher, EC
趋化因子受体（CKR）与Th 1和Th 2细胞极化和效应功能的当前概念在很大程度上忽略了体内效应和记忆T细胞的多样性。在这里，我们系统地研究了11个CKR，单独或组合，与CD 4 T细胞极化。我们表明，Th 1，Th 2，Th 0，和非极化T细胞在血液和组织中可以表达任何CKR研究，但每个CKR定义一个特征池的极化和非极化的CD 4 T细胞。CKR的某些组合定义了明显富集Th 1细胞相对于Th 2细胞的主要亚群的群体。例如，在协同表达CXCR 3和CCR 4的血液CD 4 T细胞中，Th 0、Th 1和Th 2细胞均存在，但Th 1细胞可以是CXCR 3（+）CCR 4（-），而Th 2细胞不是，而Th 2细胞是CCR 4（+）CXCR 3（-），但只有少数Th 1细胞是CCR 4（+）。与最近的报道相反，尽管CCR 7（-）细胞含有更高频率的极化CD 4 T细胞，但大多数Th 1和Th 2效应细胞是CCR 7（+），因此可能能够进行淋巴器官归巢。有趣的是，除了与CXCR 3共表达外，Th 1相关CKR对Th 1细胞几乎没有偏好。我们的结论是，CKRs的组合表达，这使得组织和亚群依赖性靶向效应细胞在趋化导航，定义生理上重要的极化和非极化T细胞的子集。
Current concepts of chemokine receptor (CKR) association with Th1 and Th2 cell polarization and effector function have largely ignored the diverse nature of effector and memory T cells in vivo. Here, we systematically investigated the association of 11 CKRs, singly or in combination, with CD4 T cell polarization. We show that Th1, Th2, Th0, and nonpolarized T cells in blood and tissue can express any of the CKRs studied but that each CKR defines a characteristic pool of polarized and nonpolarized CD4 T cells. Certain combinations of CKRs define populations that are markedly enriched in major subsets of Th1 versus Th2 cells. For example, although Th0, Th1, and Th2 cells are each found among blood CD4 T cells coordinately expressing CXCR3 and CCR4, Th1 but not Th2 cells can be CXCR3(+)CCR4(-), and Th2 but only rare Th1 cells are CCR4(+)CXCR3(-). Contrary to recent reports, although CCR7(-) cells contain a higher frequency of polarized CD4 T cells, most Th1 and Th2 effector cells are CCR7(+) and thus may be capable of lymphoid organ homing. Interestingly, Th1-associated CKRs show little or no preference for Th1 cells except when they are coexpressed with CXCR3. We conclude that the combinatorial expression of CKRs, which allow tissue- and subset-dependent targeting of effector cells during chemotactic navigation, defines physiologically significant subsets of polarized and nonpolarized T cells.