CCR7 directs the migration of thymocytes into the thymic medulla.
Developing thymocytes migrate from the cortex to the medulla of the thymus as a consequence of positive selection. This migration is likely to be essential for tolerance because it allows the developing cells to move into an environment that is optimal for negative selection. Guidance mechanisms that draw positively selected thymocytes into the medulla have not been clarified, but several studies have implicated chemokines in the process. CCR7, the receptor for the medullary chemokines CCL19 and CCL21, is induced on thymocytes during their positive selection. In this study we show that premature expression of CCR7 repositions CD4(+)CD8(+) double-positive cells into the medulla of transgenic mice. This repositioning of the thymocytes is accompanied by impairment of their development. The data show the involvement of CCR7 in medullary migration and emphasize the importance of proper thymocyte positioning for efficient T cell development.
Kwan
Joanne
J
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
Killeen
Nigel
N
D000818:Animals; D000831:Animals, Newborn; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019742:Chemokines, CC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019076:Transgenes / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; C515371:Ccr7 protein, mouse; D019742:Chemokines, CC; D008024:Ligands; D054400:Receptors, CCR7; D019707:Receptors, Chemokine