title: Direct contact between dendritic cells and bronchial epithelial cells inhibits T cell recall responses towards mite and pollen allergen extracts in vitro.
abstract: Airway epithelial cells (AECs) form a polarized barrier along the respiratory tract. They are the first point of contact with airborne antigens and are able to instruct resident immune cells to mount appropriate immune responses by either soluble or contact-dependent mechanisms. We hypothesize that a healthy, polarized epithelial cell layer inhibits inflammatory responses towards allergens to uphold homeostasis. Using an in-vitro co-culture model of the airway epithelium, where a polarized cell layer of bronchial epithelial cells can interact with dendritic cells (DCs), we have investigated recall T cell responses in allergic patients sensitized to house dust mite, grass and birch pollen. Using allergen extract-loaded DCs to stimulate autologous allergen-specific T cell lines, we show that AEC-imprinted DCs inhibit T cell proliferation significantly of Bet v 1-specific T cell lines as well as decrease interleukin (IL)-5 and IL-13 production, whereas inhibition of Phl p 5-specific T cells varied between different donors. Stimulating autologous CD4(+) T cells from allergic patients with AEC-imprinted DCs also inhibited proliferation significantly and decreased production of both T helper type 1 (Th1) and Th2 cytokines upon rechallenge. The inhibitory effects of AECs' contact with DCs were absent when allergen extract-loaded DCs had been exposed only to AECs supernatants, but present after direct contact with AECs. We conclude that direct contact between DCs and AECs inhibits T cell recall responses towards birch, grass and house dust mite allergens in vitro, suggesting that AECs-DC contact in vivo constitute a key element in mucosal homeostasis in relation to allergic sensitisation.
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense.|ALK, Global Research, Hørsholm, Denmark.
authors.forename: D
authors.initials: D
authors.lastname: Papazian
authors.affiliation: ALK, Global Research, Hørsholm, Denmark.
authors.forename: V R
authors.initials: VR
authors.lastname: Wagtmann
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense.
authors.forename: S
authors.initials: S
authors.lastname: Hansen
authors.affiliation: ALK, Global Research, Hørsholm, Denmark.
authors.forename: P A
authors.initials: PA
authors.lastname: Würtzen
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D052179:Antigens, Plant / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology; D010940:Plant Proteins / Q000276:immunology; D011058:Pollen / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D052179:Antigens, Plant; D017077:Culture Media, Conditioned; C508599:IL5 protein, human; D018793:Interleukin-13; D015848:Interleukin-5; C076049:Phl p V protein, Phleum pratense; D010936:Plant Extracts; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula
keywords: T cells; allergy; dendritic cells; human; mucosa; tolerance