title: CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha.
abstract: CC-chemokine receptor (CCR) 6 is the only known receptor for macrophage inflammatory protein (MIP)-3alpha, a CC chemokine chemotactic for lymphocytes and dendritic cells. Using anti-serum that we raised against the N-terminal residues of CCR6, we have characterized the surface expression of CCR6 on peripheral blood leukocytes and we have correlated CCR6 expression with responses to MIP-3alpha. We found that CCR6 was expressed only on memory T cells, including most alpha4beta7 memory cells and cutaneous lymphocyte-associated Ag-expressing cells, and on B cells. Accordingly, chemotaxis of T cells to MIP-3alpha was limited to memory cells. Moreover, calcium signals on T cells in response to MIP-3a were confined to CCR6-expressing cells, consistent with CCR6 being the only MIP-3alpha receptor on peripheral blood T cells. Unlike many CC chemokines, MIP-3alpha produced a calcium signal on freshly isolated T cells, and CCR6 expression was not increased by up to 5 days of treatment with IL-2 or by cross-linking CD3. Despite their surface expression of CCR6, freshly isolated B cells did not respond to MIP-3alpha. In addition to staining peripheral blood leukocytes, our anti-serum detected CCR6 on CD34+ bone marrow cell-derived dendritic cells. Our data are the first to analyze surface expression of CCR6, demonstrating receptor expression on differentiated, resting memory T cells, indicating differences in receptor signaling on T cells and B cells and suggesting that CCR6 and MIP-3alpha may play a role in the physiology of resting memory T cells and in the interactions of memory T cells, B cells, and dendritic cells.
authors.affiliation: Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: F
authors.initials: F
authors.lastname: Liao
authors.forename: R L
authors.initials: RL
authors.lastname: Rabin
authors.forename: C S
authors.initials: CS
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Sharma
authors.forename: T B
authors.initials: TB
authors.lastname: Nutman
authors.forename: J M
authors.initials: JM
authors.lastname: Farber
mesh_terms: D002460:Cell Line; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007106:Immune Sera / Q000096:biosynthesis; D007156:Immunologic Memory; D007668:Kidney / Q000166:cytology; D007962:Leukocytes / Q000737:chemistry / Q000276:immunology; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins; D010446:Peptide Fragments / Q000276:immunology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D007106:Immune Sera; D019402:Macrophage Inflammatory Proteins; D010446:Peptide Fragments; D054399:Receptors, CCR6; D019707:Receptors, Chemokine