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/jci200113543
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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
目前关于趋化因子受体(CKR)与Th1和Th2细胞极化和效应器功能相关的概念在很大程度上忽略了体内效应器和记忆性T细胞的多样性。在这里，我们系统地研究了11个CKR单独或联合与CD4T细胞极化的关系。我们发现，血液和组织中的Th1、Th2、Th0和非极化T细胞可以表达所研究的任何CKR，但每个CKR定义了极化和非极化的CD4T细胞的特征池。CKRs的某些组合定义了在Th1和Th2细胞的主要亚群中明显丰富的人群。例如，虽然在协调表达CXCR3和CCR4的血液CD4T细胞中分别存在Th0、Th1和Th2细胞，但Th1而不是Th2细胞可以是CXCR3(+)CCR4(-)，而Th2但只有罕见的Th1细胞是CCR4(+)CXCR3(-)。与最近的报道相反，尽管CCR7(-)细胞含有更高频率的极化的CD4T细胞，但大多数Th1和Th2效应细胞是CCR7(+)，因此可能具有淋巴器官归巢的能力。有趣的是，Th1相关的CKRs很少或根本不偏好Th1细胞，除非它们与CXCR3共表达。我们的结论是，CKRs的组合表达，允许在趋化导航过程中依赖于组织和亚群的靶向效应细胞，定义了极化和非极化T细胞的生理意义亚群。
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.