title: Virus stimulation of human mast cells results in the recruitment of CD56⁺ T cells by a mechanism dependent on CCR5 ligands.
abstract: The trafficking of effector cells to sites of infection is crucial for antiviral responses. However, the mechanisms of recruitment of the interferon-γ-producing and cytotoxic CD56(+) T cells are poorly understood. Human mast cells are sentinel cells found in the skin and airway and produce selected proinflammatory mediators in response to multiple pathogen-associated signals. The role of human mast cell-derived chemokines in T-cell recruitment to virus infection was examined. Supernatants from primary human cord blood-derived mast cells (CBMCs) infected with mammalian reovirus were examined for chemokine production and utilized in chemotaxis assays. Virus-infected CBMCs produced several chemokines, including CCL3, CCL4, and CCL5. Supernatants from reovirus-infected CBMCs selectively induced the chemotaxis of CD8(+) T cells (10±1%) and CD3(+)CD56(+) T cells (19±5%). CD56(+) T-cell migration was inhibited by pertussis toxin (65±9%) and met-RANTES (56±7%), a CCR1/CCR5 antagonist. CD56(+) T cells expressed CCR5, but little CCR1. The depletion of CCL3, CCL4, and CCL5 from reovirus-infected CBMC supernatants significantly (41±10%) inhibited CD56(+) T-cell chemotaxis. This study demonstrates a novel role for mast cells and CCR5 in CD56(+) T-cell trafficking and suggests that human mast cells enhance immunity to viruses through the selective recruitment of cytotoxic effector cells to virus infection sites. These findings could be exploited to enhance local T-cell responses in chronic viral infection and malignancies at mast cell-rich sites.
authors: Dalhousie Inflammation Group, Dalhousie University, 5850 College St., Halifax, NS B3H 1X5, Canada.
authors: Sarah M
authors: SM
authors: McAlpine
authors: Thomas B
authors: TB
authors: Issekutz
authors: Jean S
authors: JS
authors: Marshall
mesh_terms: D019002:CD56 Antigen / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D054407:Chemokine CCL4 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D018925:Chemokines / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008024:Ligands; D012089:Mammalian orthoreovirus 3 / Q000276:immunology* / Q000502:physiology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D019002:CD56 Antigen; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D017077:Culture Media, Conditioned; D008024:Ligands; C522918:NCAM1 protein, human; C108335:RANTES, Met-; D019713:Receptors, CCR5