title: Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets.
abstract: In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16(+), CD1c(+), and BDCA-3(+) myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8(+) T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c(+) and BDCA3(+) mDCs, pDCs induce potent Ag-specific CD4(+) and CD8(+) T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4(+) and CD8(+) T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3(+) mDCs. These findings, and the fact that pDCs outnumber BDCA3(+) mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8(+) T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jurjen
authors.initials: J
authors.lastname: Tel
authors.forename: Gerty
authors.initials: G
authors.lastname: Schreibelt
authors.forename: Simone P
authors.initials: SP
authors.lastname: Sittig
authors.forename: Till S M
authors.initials: TS
authors.lastname: Mathan
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Buschow
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Cruz
authors.forename: Annechien J A
authors.initials: AJ
authors.lastname: Lambeck
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D012995:Solubility; D018180:Thrombomodulin
chemical_list: D018949:Antigens, CD1; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C437944:CD1C protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D017452:Receptors, IgG; C546931:THBD protein, human; D018180:Thrombomodulin; D007371:Interferon-gamma