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Differential contribution of chemotaxis and substrate restriction to segregation of immature and mature thymocytes.

ABSTRACT: 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 (SP) 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 SP 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.

SUBMITTER: Ehrlich LI

PROVIDER: S-EPMC4106268 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Differential contribution of chemotaxis and substrate restriction to segregation of immature and mature thymocytes.

Ehrlich Lauren I Richie LI Oh David Y DY Weissman Irving L IL Lewis Richard S RS

Immunity 20091203 6

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 specia ...[more]

PMID: 19962328

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Dataset Information

Differential contribution of chemotaxis and substrate restriction to segregation of immature and mature thymocytes.

Publications

Differential contribution of chemotaxis and substrate restriction to segregation of immature and mature thymocytes.

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