title: Macrophage-derived chemokine is localized to thymic medullary epithelial cells and is a chemoattractant for CD3(+), CD4(+), CD8(low) thymocytes.
abstract: Macrophage-derived chemokine (MDC) is a recently identified CC chemokine that is a potent chemoattractant for dendritic cells, natural killer (NK) cells, and the Th2 subset of peripheral blood T cells. In normal tissues, MDC mRNA is expressed principally in the thymus. Immunohistochemical analysis performed on 5 human postnatal thymuses showed high MDC immunoreactivity, which was selectively localized to epithelial cells within the medulla. To examine the effects of MDC on immature T cells, we have identified cDNA clones for mouse and rat MDC. Expression of MDC in murine tissues is also highly restricted, with significant levels of mRNA found only in the thymus. Thymocytes express high-affinity binding sites for MDC (kd = 0.7 nmol/L), and, in vitro, MDC is a chemoattractant for these cells. MDC-responsive murine thymocytes express mRNA for CCR4, a recently identified receptor for MDC. Phenotypic analysis of MDC-responsive cells shows that they are enriched for a subset of double-positive cells that express high levels of CD3 and CD4 and that have reduced levels of CD8. This subset of MDC-responsive cells is consistent with the observed expression of MDC within the medulla, because more mature cells are found there. MDC may therefore play a role in the migration of T-cell subsets during development within the thymus.
authors.affiliation: ICOS Corp, Bothell, WA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chantry
authors.forename: P
authors.initials: P
authors.lastname: Romagnani
authors.forename: C J
authors.initials: CJ
authors.lastname: Raport
authors.forename: C L
authors.initials: CL
authors.lastname: Wood
authors.forename: A
authors.initials: A
authors.lastname: Epp
authors.forename: S
authors.initials: S
authors.lastname: Romagnani
authors.forename: P W
authors.initials: PW
authors.lastname: Gray
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010802:Phylogeny; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: C515482:CCL22 protein, human; D017252:CD3 Complex; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D019742:Chemokines, CC