Characterization of CCR9 expression and CCL25/thymus-expressed chemokine responsiveness during T cell development: CD3(high)CD69+ thymocytes and gammadeltaTCR+ thymocytes preferentially respond to CCL25.
CCR9 mediates chemotaxis of thymocytes in response to CCL25/thymus-expressed chemokine, and its mRNA is selectively expressed in thymus and small intestine, the two known sites of T lymphopoiesis. To examine the expression of CCR9 during lymphocyte development, we generated polyclonal Ab that recognizes murine CCR9. CCR9 was expressed on the majority of immature CD4+CD8+ (double-positive) thymocytes, but not on immature CD4(-)CD8(-) (double-negative) thymocytes. CCR9 was down-regulated during the transition of double-positive thymocytes to the CD4+ or CD8+ (single-positive) stage, and only a minor subset of CD8+ lymph node T cells expressed CCR9. All CCR9+ thymocyte subsets migrated in response to CCL25; however, CD69+ thymocytes demonstrated enhanced CCL25-induced migration compared with CD69(-) thymocytes. Ab-mediated TCR stimulation also enhanced CCL25 responsiveness, indicating that CCL25-induced thymocyte migration is augmented by TCR signaling. Approximately one-half of all gammadeltaTCR+ thymocytes and peripheral gammadeltaTCR+ T cells expressed CCR9 on their surface, and these cells migrated in response to CCL25. These findings suggest that CCR9 may play an important role in the development and trafficking of both alphabetaTCR+ and gammadeltaTCR+ T cells.
Uehara
Shoji
S
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Song
Kaimei
K
Farber
Joshua M
JM
Love
Paul E
PE
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D019070:Cell Lineage; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D005260:Female; D016130:Immunophenotyping; D007421:Intestine, Small / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000254:growth & development / Q000276:immunology*; D000099192:CD69 Antigens
D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019742:Chemokines, CC; D037181:Lectins, C-Type; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D000099192:CD69 Antigens; C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse