Molecular mechanisms of cell migration during T-lymphocyte development

这项研究的目的是确定在胸腺T淋巴细胞发育过程中控制细胞迁移的分子。我们的结果表明：(1)胸腺上皮细胞分泌的两种趋化因子CCL21和CCL25在吸引T淋巴祖细胞进入胎儿胸腺中起主要作用。我们还发现(2)通过CCL19/CCL21和CCR7的趋化因子信号本质上调节了阳性选择的胸腺细胞从胸腺皮质到胸腺髓质的迁移。研究表明，发育中的胸腺细胞依赖趋化因子从皮质到髓质的迁移是建立对组织特异性抗原的中枢耐受所必需的，而不是对成人胸腺的T细胞成熟或T细胞输出所必需的。此外，我们的研究表明，在新生小鼠中，胸腺成熟T淋巴细胞的迁移依赖于CCR7趋化因子信号，而在成年小鼠中则不是。这些结果有助于更好地理解在胸腺T淋巴细胞发育过程中控制细胞迁移的分子机制。

This study was aimed to identify the molecules that govern cellular migration during T-lymphocyte development in the thymus. Our results showed that (1)two chemokines CCL21 and CCL25, which are secreted by thymic epithelial cells, play a major role in attracting T-lymphoid progenitor cells to fetal thymus. We also showed that (2)chemokine signals via CCL19/CCL21 and CCR7 essentially regulate the migration of positively selected thymocytes from the thymic cortex to the thymic medulla. It was identified that the chemokine-dependent cortex-to-medulla migration of developing thymocytes was essential for establishment of central tolerance to tissue-specific antigens and not for T-cell maturation or T-cell export from adult thymus. Furthermore, our study showed that the emigration of mature T lymphocytes from the thymus was dependent on CCR7 chemokine signals in newborn mice but not in adult mice. These results have contributed to better understanding of molecular mechanisms that govern cellular migration during T-lymphocyte development in the thymus.