In vivo differentiated cytokine-producing CD4+ T cells express functional CCR7
In vivo differentiated cytokine-producing CD4+ T cells express functional CCR7
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DOI：
10.4049/jimmunol.168.11.5441
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发表时间：
2002-06-01
影响因子：
4.4
通讯作者：
Hamann, A
中科院分区：
文献类型：
--
作者：
Debes, GF;Höpken, UE;Hamann, A
趋化因子及其受体在炎症和稳态条件下发挥专门作用。CCR 7及其配体CCL 19和CCL 21参与通过次级淋巴器官的淋巴细胞再循环，并且另外将淋巴细胞导航到不同的组织区室中。CCR 7在体内极化T效应/记忆细胞亚群迁移中的作用仍然知之甚少。因此，我们分析了小鼠和人的CD 4（+）的精氨酸生产细胞在体内开发的趋化反应，CCR 7配体。产生细胞因子（如IFN-γ、IL-4和IL-10）的细胞以及由记忆或活化标记物定义的亚群的反应与初始CD 4（+）细胞的反应相当，表达IL-10或CD 69的细胞的反应性略低。这表明CCR 7配体能够吸引幼稚以及绝大多数活化和效应/记忆T细胞阶段。这些细胞对CCL 21的趋化反应性在CCR 7缺陷细胞中不存在，证明效应细胞不使用该趋化因子的替代受体。从CCR 7（-/-）小鼠产生的Th 1细胞未能进入淋巴结和派伊尔集合淋巴结，但确实进入了炎症部位。这些发现表明，在刺激后产生效应细胞因子的CD 4（+）细胞保留了通过CCR 7通过淋巴组织再循环的能力。
Chemokines and their receptors fulfill specialized roles in inflammation and under homeostatic conditions. CCR7 and its ligands, CCL19 and CCL21, are involved in lymphocyte recirculation through secondary lymphoid organs and additionally navigate lymphocytes into distinct tissue compartments. The role of CCR7 in the migration of polarized T effector/memory cell subsets in vivo is still poorly understood. We therefore analyzed murine and human CD4(+) cytokine-producing cells developed in vivo for their chemotactic reactivity to CCR7 ligands. The responses of cells producing cytokines, such as IFN-gamma, IL-4, and IL-10, as well as of subsets defined by memory or activation markers were comparable to that of naive CD4(+) cells, with slightly lower reactivity in cells expressing IL-10 or CD69. This indicates that CCR7 ligands are able to attract naive as well as the vast majority of activated and effector/memory T cell stages. Chemotactic reactivity of these cells toward CCL21 was absent in CCR7-deficient cells, proving that effector cells do not use alternative receptors for this chemokine. Th1 cells generated from CCR7(-/-) mice failed to enter lymph nodes and Peyer's patches, but did enter a site of inflammation. These findings indicate that CD4(+) cells producing effector cytokines upon stimulation retain the capacity to recirculate through lymphoid tissues via CCR7.