Cutting edge: developmental switches in chemokine responses during T cell maturation.
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.
Campbell
J J
JJ
Laboratory of Immunology and Vascular Biology, Department of Pathology, Digestive Disease Center, Stanford University Medical School, CA 94305, USA.
Pan
J
J
Butcher
E C
EC
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D054414:Chemokine CCL17; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054422:Chemokine CCL22; D054377:Chemokine CXCL12; D018925:Chemokines / Q000096:biosynthesis* / Q000502:physiology; D019742:Chemokines, CC / Q000502:physiology; D019743:Chemokines, CXC / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D051379:Mice; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
C499538:Ccl17 protein, mouse; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515483:Ccl22 protein, mouse; C491541:Ccl25 protein, mouse; C515355:Ccr4 protein, mouse; C515371:Ccr7 protein, mouse; D054414:Chemokine CCL17; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054422:Chemokine CCL22; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D019707:Receptors, Chemokine