Differential Contribution of Chemotaxis and Substrate Restriction to Segregation of Immature and Mature Thymocytes

被引:85
作者
Ehrlich, Lauren I. Richie [1 ]
Oh, David Y. [2 ]
Weissman, Irving L. [1 ]
Lewis, Richard S. [2 ]
机构
[1] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA
关键词
COMMON LYMPHOID PROGENITORS; PROMISCUOUS GENE-EXPRESSION; THYMIC EPITHELIAL-CELLS; POSITIVELY SELECTED THYMOCYTES; PERTUSSIS TOXIN; CCR7; LIGANDS; BONE-MARROW; NEGATIVE SELECTION; MEDULLA MIGRATION; CENTRAL TOLERANCE;
D O I
10.1016/j.immuni.2009.09.020
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:986 / 998
页数:13
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