title: CD70-CD27 interaction augments CD8+ T-cell activation by human epidermal Langerhans cells.
abstract: Human cutaneous dendritic cells (DCs) from epidermal and dermal compartments exhibit functional differences in their induction of CD4+ T-cell and humoral immune responses; however, differences in the regulation of memory CD8+ T-cell responses by human skin DCs remain poorly characterized. We tested the capacity of human Langerhans cells (LCs) and dermal dendritic cells (DDCs) to induce antigen-specific cytokine production and proliferation of memory CD8+ cells. Although tumor necrosis factor-α-matured human DCs from both epidermal and dermal compartments showed efficient potential to activate CD8+ cells, LCs were constitutively more efficient than DDCs in cross-presenting CD8+ epitopes, as well as direct presentation of viral antigen to Epstein-Barr virus-specific CD8+ T cells. LCs showed greater expression of CD70, and blockade of CD70-CD27 signaling demonstrated that superiority of CD8+ activation by epidermal LC is CD70 dependent. This CD70-related activation of CD8+ cells by LCs denotes a central role of LCs in CD8+ immunity in skin, and suggests that regulation of LC CD70 expression is important in enhancing immunity against cutaneous epithelial pathogens and cancer.
authors.affiliation: Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Polak
authors.forename: Louise
authors.initials: L
authors.lastname: Newell
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Taraban
authors.forename: Christopher
authors.initials: C
authors.lastname: Pickard
authors.forename: Eugene
authors.initials: E
authors.lastname: Healy
authors.forename: Peter S
authors.initials: PS
authors.lastname: Friedmann
authors.forename: Aymen
authors.initials: A
authors.lastname: Al-Shamkhani
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ardern-Jones
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D053282:CD27 Ligand / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D053282:CD27 Ligand; C505771:CD70 protein, human; D016207:Cytokines; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha