High endothelial venules (HEVs) effectively recruit circulating lymphocytes from the blood to lymph nodes. HEVs have endothelial cells (ECs) and perivascular sheaths consisting of fibroblastic reticular cells (FRCs). Yet, post-luminal lymphocyte migration steps are not well elucidated. Herein, we performed intravital imaging to investigate post-luminal T- and B-cell migration in popliteal lymph node, consisting of trans-EC migration, crawling in the perivascular channel (a narrow space between ECs and FRCs) and trans-FRC migration. The post-luminal migration of T cells occurred in a PNAd-dependent manner. Remarkably, we found hot spots for the trans-EC and trans-FRC migration of T- and B cells. Interestingly, T- and B cells preferentially shared trans-FRC migration hot spots but not trans-EC migration hot spots. Furthermore, the trans-FRC T-cell migration was confined to fewer sites than trans-EC T-cell migration, and trans-FRC migration of T- and B cells preferentially occurred at FRCs covered by CD11c+ dendritic cells in HEVs. These results suggest that HEV ECs and FRCs with perivascular DCs delicately regulate T- and B-cell entry into peripheral lymph nodes.

中文翻译：

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T 细胞和 B 细胞通过高内皮微静脉中的血管周围通道逐步迁移。

高内皮小静脉 (HEV) 有效地将循环淋巴细胞从血液中募集到淋巴结。HEV 具有内皮细胞 (EC) 和由成纤维细胞网状细胞 (FRC) 组成的血管周围鞘。然而，管腔后淋巴细胞迁移步骤尚未得到很好的阐明。在此，我们进行了活体成像以研究腘淋巴结中的管腔后 T 细胞和 B 细胞迁移，包括跨 EC 迁移、在血管周围通道（EC 和 FRC 之间的狭窄空间）中爬行和跨 FRC 迁移。T 细胞的管腔后迁移以 PNAd 依赖性方式发生。值得注意的是，我们发现了 T 细胞和 B 细胞的跨 EC 和跨 FRC 迁移的热点。有趣的是，T 细胞和 B 细胞优先共享跨 FRC 迁移热点而不是跨 EC 迁移热点。此外，与跨 EC T 细胞迁移相比，跨 FRC T 细胞迁移局限于更少的位点，并且 T 细胞和 B 细胞的跨 FRC 迁移优先发生在 HEV 中被 CD11c+ 树突细胞覆盖的 FRC。这些结果表明，具有血管周围 DC 的 HEV EC 和 FRC 精细调节 T 细胞和 B 细胞进入外周淋巴结。