Differential Contribution of Chemotaxis and Substrate Restriction to Segregation of Immature and Mature Thymocytes
Differential Contribution of Chemotaxis and Substrate Restriction to Segregation of Immature and Mature Thymocytes
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DOI：
10.1016/j.immuni.2009.09.020
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发表时间：
2009-12-18
期刊：
影响因子：
32.4
通讯作者：
Lewis, Richard S.
中科院分区：
文献类型：
--
作者：
Ehrlich, Lauren I. Richie;Oh, David Y.;Lewis, Richard S.
T细胞发育需要胸腺细胞亚群顺序定位到不同的胸腺微环境。为了解决这种分离的机制，我们使用双光子显微镜观察纯化的胸腺细胞亚群在胸腺切片内定义的微环境中的迁移。双阴性（CD 4（-）8）和双阳性（CD 4（+）8（+））胸腺细胞局限于皮质，在那里它们移动缓慢，没有方向性偏差。DP细胞积累和迁移更迅速地在一个专门的内皮层微环境，但不能迁移到髓质基质。相反，CD 4单阳性（SIP）胸腺细胞向髓质方向迁移，在那里他们积累和移动非常迅速。我们的研究结果揭示了一个必要的两个步骤的过程中，管理CD 4 SP细胞髓质定位：趋化因子受体CCR 7介导的趋化性CD 4 SIP细胞向髓质，而一个独特的百日咳毒素敏感的通路需要进入髓质。这些发现表明，发育调节反应的趋化信号和特定的迁移基板指导胸腺细胞在胸腺的特定位置。
T cell development requires sequential localization of thymocyte subsets to distinct thymic microenvironments. To address mechanisms governing this segregation, we used two-photon microscopy to visualize migration of purified thymocyte subsets in defined microenvironments within thymic slices. Double-negative (CD4(-)8) and double-positive (CD4(+)8(+)) thymocytes were confined to cortex where they moved slowly without directional bias. DP cells accumulated and migrated more rapidly in a specialized inner-cortical microenvironment, but were unable to migrate on medullary substrates. In contrast, CD4 single positive (SIP) thymocytes migrated directionally toward the medulla, where they accumulated and moved very rapidly. Our results revealed a requisite two-step process governing CD4 SP cell medullary localization: the chemokine receptor CCR7 mediated chemotaxis of CD4 SIP cells towards medulla, whereas a distinct pertussis-toxin sensitive pathway was required for medullary entry. These findings suggest that developmentally regulated responses to both chemotactic signals and specific migratory substrates guide thymocytes to specific locations in the thymus.