Campbell J J, Pan J, Butcher E C
Laboratory of Immunology and Vascular Biology, Department of Pathology, Digestive Disease Center, Stanford University Medical School, CA 94305, USA.
J Immunol. 1999 Sep 1;163(5):2353-7.
We show that developmental transitions during thymocyte maturation are associated with dramatic changes in chemotactic responses to chemokines. Macrophage-derived chemokine, a chemokine expressed in the thymic medulla, attracts thymocytes only during a brief window of development, between the late cortical and early medullary stages. All medullary phenotypes (CD4 or CD8 single positive) but not immature thymocytes respond to the medullary stroma-expressed (and secondary lymphoid tissue-associated) chemokines secondary lymphoid-tissue chemokine and macrophage inflammatory protein-3beta. The appearance of these responses is associated with the phenotypic stage of cortex to medulla migration and with up-regulation of mRNA for the receptors CCR4 (for macrophage-derived chemokine and thymus and activation-regulated chemokine) and CCR7 (for secondary lymphoid-tissue chemokine and macrophage inflammatory protein-3beta). In contrast, most immature and medullary thymocytes migrate to thymus-expressed chemokine, an ability that is lost only with up-regulation of the peripheral homing receptor L-selectin during the latest stages of thymocyte maturation associated with export to the periphery. Developmental switches in chemokine responses may help regulate critical migratory events during T cell development.
我们发现，胸腺细胞成熟过程中的发育转变与趋化因子趋化反应的显著变化相关。巨噬细胞衍生趋化因子是一种在胸腺髓质中表达的趋化因子，仅在发育的一个短暂窗口期，即皮质晚期和髓质早期之间吸引胸腺细胞。所有髓质表型（CD4或CD8单阳性）而非未成熟胸腺细胞对髓质基质表达的（以及与二级淋巴组织相关的）趋化因子二级淋巴组织趋化因子和巨噬细胞炎性蛋白-3β有反应。这些反应的出现与从皮质向髓质迁移的表型阶段以及受体CCR4（针对巨噬细胞衍生趋化因子和胸腺激活调节趋化因子）和CCR7（针对二级淋巴组织趋化因子和巨噬细胞炎性蛋白-3β）的mRNA上调有关。相比之下，大多数未成熟和髓质胸腺细胞迁移至胸腺表达的趋化因子，这种能力仅在胸腺细胞成熟的最后阶段与向外周输出相关的外周归巢受体L-选择素上调时丧失。趋化因子反应中的发育转换可能有助于调节T细胞发育过程中的关键迁移事件。
