title: Human plasmacytoid dendritic cells are equipped with antigen-presenting and tumoricidal capacities.
abstract: Human plasmacytoid dendritic cells (pDCs) represent a highly specialized naturally occurring dendritic-cell subset and are the main producers of type I interferons (IFNs) in response to viral infections. We show that human pDCs activated by the preventive vaccine FSME specifically up-regulate CD56 on their surface, a marker that was thought to be specific for NK cells and associated with cytolytic effector functions. We observed that FSME-activated pDCs specifically lysed NK target cells and expressed cytotoxic molecules, such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and granzyme B. Elevated levels of these molecules coincided with the expression of CD56, indicative for skewing human pDCs toward an interferon-producing killer DC subset. Detailed phenotypical and functional analysis revealed that pDCs attained a mature phenotype, secreted proinflammatory cytokines, and had the capacity to present antigens and stimulate T cells. Here, we report on the generation of CD56(+) human interferon producing killer pDCs with the capacity to present antigens. These findings aid in deciphering the role for pDCs in antitumor immunity and present a promising prospect of developing antitumor therapy using pDCs.
authors.affiliation: Department of Tumor Immunology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Jurjen
authors.initials: J
authors.lastname: Tel
authors.forename: Evelien L
authors.initials: EL
authors.lastname: Smits
authors.forename: Sébastien
authors.initials: S
authors.lastname: Anguille
authors.forename: Rubin N
authors.initials: RN
authors.lastname: Joshi
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D060890:B7-H1 Antigen / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014612:Vaccines / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D019002:CD56 Antigen; D053221:TNF-Related Apoptosis-Inducing Ligand; D014612:Vaccines; D053804:Granzymes