Cutting edge: developmental switches in chemokine responses during T cell maturation.

Cutting edge: developmental switches in chemokine responses during T cell maturation.
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DOI:
10.4049/jimmunol.163.5.2353
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发表时间:
1999-09
影响因子:
4.4
通讯作者:
James J. Campbell;Junliang Pan;E. Butcher
James J. Campbell;Junliang Pan;E. Butcher
中科院分区:
医学2区
文献类型:
--
作者:
James J. Campbell;Junliang Pan;E. Butcher

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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巨大变化有关。巨噬细胞源性趋化因子是一种在胸腺髓质中表达的趋化因子,仅在皮质晚期和髓质早期之间的短暂发育窗口期吸引胸腺细胞。所有髓质表型(CD 4或CD 8单阳性)但不成熟胸腺细胞对髓质基质表达(和次级淋巴组织相关)趋化因子次级淋巴组织趋化因子和巨噬细胞炎性蛋白-3 β有反应。这些反应的出现与皮质向髓质迁移的表型阶段以及受体CCR 4(巨噬细胞衍生趋化因子和胸腺活化调节趋化因子)和CCR 7(次级淋巴组织趋化因子和巨噬细胞炎性蛋白-3 β)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到胸腺表达的趋化因子,只有在与出口到外周相关的胸腺细胞成熟的最后阶段,外周归巢受体L-选择素的上调才失去这种能力。趋化因子反应中的发育开关可能有助于调节T细胞发育过程中的关键迁移事件。
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.