CXC Chemokine Ligand 12 Promotes CCR7-Dependent Naive T Cell Trafficking to Lymph Nodes and Peyer's Patches
CXC Chemokine Ligand 12 Promotes CCR7-Dependent Naive T Cell Trafficking to Lymph Nodes and Peyer's Patches
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DOI：
10.4049/jimmunol.182.3.1287
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发表时间：
2009-02-01
影响因子：
4.4
通讯作者：
Miyasaka, Masayuki
中科院分区：
文献类型：
--
作者：
Bai, Zhongbin;Hayasaka, Haruko;Miyasaka, Masayuki
许多趋化因子，包括 CCL21、CCL19、CXCL12 和 CXCL13，在淋巴结 (LN) 和派尔氏淋巴结 (PP) 的高内皮微静脉 (HEV) 的管腔或基底层上共表达，这与它们可能合作调节淋巴细胞运输到这些淋巴组织的观点一致。在这项研究中，我们报告说，CXCL12 通过其受体 CXCR4 发挥作用，与 CCR7 配体合作促进 T 细胞跨 HEV 运输。 CXCL12。在 CCR7 配体的次优浓度下，在体外增强了 CCR7 诱导的野生型而非 CXCR4 缺陷型 T 细胞的趋化性，但不影响 CCR7 的表达水平或配体结合能力。实时趋化性分析表明，CXCL12 显着缩短了体外细胞迁移开始前的滞后时间，但并未缩短 T 细胞响应次优 CCR7 配体浓度的迁移速度。此外，在相同条件下，CXCL12 增强了 T 细胞中 CCR7 配体驱动的 ERK 磷酸化和肌动蛋白聚合。在过继转移实验中，CXCL12 促进了野生型而非 CCR7 配体缺陷 plt/plt 受体小鼠中幼稚 T 细胞向 LN 和 PP 的运输； T 细胞运输的增加与 T 细胞与 HEV 的结合增强以及随后迁移到淋巴结实质有关。因此，CXCL12 与 CCR7 配体协同作用，通过 CXCR4 使 T 细胞敏感，从而促进 T 细胞迁移，从而使它们能够对较低浓度的 CCR7 配体做出反应。趋化因子的这种协同作用提供了一种额外的、以前未知的机制，用于有效地将淋巴细胞跨 HEV 运输到 LN 和 PP。免疫学杂志，2009，182：1287-1295。
A number of chemokines, including CCL21, CCL19, CXCL12, and CXCL13, are coexpressed on the lumen or basal lamina of high endothelial venules (HEVs) in lymph nodes (LNs) and Peyer's patches (PPs), consistent with the idea that they might cooperate to regulate lymphocyte trafficking into these lymphoid tissues. In this study we report that CXCL12, acting through its receptor, CXCR4, cooperates with CCR7 ligands to promote T cell trafficking across HEVs. CXCL12. enhanced the CCR7-induced chemotaxis of wild-type but not CXCR4-deficient T cells in vitro at suboptimal concentrations of a CCR7 ligand, but without affecting the expression level or ligand-binding ability of CCR7. Real-time chemotaxis analysis showed that CXCL12 substantially shortened the lag time before cell migration began in vitro, but not the migration speed of T cells responding to suboptimal CCR7 ligand concentrations. In addition, CXCL12 augmented the CCR7 ligand-driven ERK phosphorylation and actin polymerization in T cells under the same conditions. In adoptive transfer experiments, CXCL12 promoted naive T cell trafficking to LNs and PPs in wild-type but not CCR7 ligand-deficient plt/plt recipient mice; this increased T cell trafficking was associated with enhanced binding of the T cells to HEVs and their subsequent migration into the LN parenchyma. Thus, CXCL12 synergizes with CCR7 ligands to promote T cell migration by sensitizing T cells through CXCR4, thus enabling them to respond to lower concentrations of CCR7 ligands. Such concerted action of chemokines provides an additional, previously unknown mechanism for efficient lymphocyte trafficking across HEVs into LNs and PPs. The Journal of Immunology, 2009, 182: 1287-1295.