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

J Immunol. 1999 Sep 1;163(5):2353-7.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Chemokine CCL17
  • Chemokine CCL19
  • Chemokine CCL21
  • Chemokine CCL22
  • Chemokine CXCL12
  • Chemokines / biosynthesis*
  • Chemokines / physiology
  • Chemokines, CC / physiology
  • Chemokines, CXC / physiology
  • Chemotaxis, Leukocyte / immunology*
  • Mice
  • Receptors, CCR4
  • Receptors, CCR7
  • Receptors, Chemokine / metabolism
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • Ccl17 protein, mouse
  • Ccl19 protein, mouse
  • Ccl21c protein, mouse
  • Ccl22 protein, mouse
  • Ccl25 protein, mouse
  • Ccr4 protein, mouse
  • Ccr7 protein, mouse
  • Chemokine CCL17
  • Chemokine CCL19
  • Chemokine CCL21
  • Chemokine CCL22
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CC
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Receptors, CCR4
  • Receptors, CCR7
  • Receptors, Chemokine