Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.
Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.
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DOI：
10.1084/jem.187.6.875
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发表时间：
1998-03-16
期刊：
影响因子：
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通讯作者：
Lanzavecchia A
中科院分区：
文献类型：
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作者：
Sallusto F;Lenig D;Mackay CR;Lanzavecchia A
趋化因子及其受体是选择性吸引各种白细胞亚群的重要元素。为了更好地了解 T 细胞功能亚群的选择性迁移，使用单克隆抗体、RNase 保护测定以及对不同趋化因子的反应来分析趋化因子受体表达。初始T细胞仅表达CXC趋化因子受体(CXCR)4，而大多数记忆/激活T细胞表达CXCR3，一小部分表达CC趋化因子受体(CCR)3和CCR5。当分析极化 T 细胞系时，发现 CXCR3 在 T 辅助细胞 (Th)0 和 Th1 上高水平表达，在 Th2 上低水平表达。相比之下，CCR3 和 CCR4 在 Th2 上发现。功能反应证实了这一点：只有 Th2 对 CCR3 和 CCR4 激动剂嗜酸细胞趋化因子和胸腺以及活化调节趋化因子 (TARC) 的 [Ca2+]i 增加做出反应，而只有 Th0 和 Th1 对低浓度的 CXCR3 激动剂 IFN-γ 诱导蛋白 10 (IP-10) 和 IFN-γ 诱导的单核因子 (Mig) 做出反应。尽管 CCR5 在 Th1 和 Th2 细胞系上均表达，但在几个 Th2 克隆中不存在，并且其表达受到白细胞介素 2 的显着影响。趋化因子受体表达以及与 Th1 和 Th2 表型的关联受到极化过程中存在的其他细胞因子的影响。转化生长因子β抑制CCR3，但增强CCR4和CCR7的表达，而干扰素α抑制CCR3，但上调CXCR3和CCR1。这些结果证明趋化因子受体是初始和极化 T 细胞亚群的标记，并表明趋化因子受体基因表达的灵活程序可以控制效应 T 细胞的组织特异性迁移。
Chemokines and their receptors are important elements for the selective attraction of various subsets of leukocytes. To better understand the selective migration of functional subsets of T cells, chemokine receptor expression was analyzed using monoclonal antibodies, RNase protection assays, and the response to distinct chemokines. Naive T cells expressed only CXC chemokine receptor (CXCR)4, whereas the majority of memory/activated T cells expressed CXCR3, and a small proportion expressed CC chemokine receptor (CCR)3 and CCR5. When polarized T cell lines were analyzed, CXCR3 was found to be expressed at high levels on T helper cell (Th)0s and Th1s and at low levels on Th2s. In contrast, CCR3 and CCR4 were found on Th2s. This was confirmed by functional responses: only Th2s responded with an increase in [Ca2+]i to the CCR3 and CCR4 agonists eotaxin and thymus and activation regulated chemokine (TARC), whereas only Th0s and Th1s responded to low concentrations of the CXCR3 agonists IFN-γ–inducible protein 10 (IP-10) and monokine induced by IFN-γ (Mig). Although CCR5 was expressed on both Th1 and Th2 lines, it was absent in several Th2 clones and its expression was markedly influenced by interleukin 2. Chemokine receptor expression and association with Th1 and Th2 phenotypes was affected by other cytokines present during polarization. Transforming growth factor β inhibited CCR3, but enhanced CCR4 and CCR7 expression, whereas interferon α inhibited CCR3 but upregulated CXCR3 and CCR1. These results demonstrate that chemokine receptors are markers of naive and polarized T cell subsets and suggest that flexible programs of chemokine receptor gene expression may control tissue-specific migration of effector T cells.