title: Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens.
abstract: The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141+ DC subset. CD141+ DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-beta, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c+ DC subset. Polyinosine-polycytidylic acid (poly I:C)-activated CD141+ DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8+ cytotoxic T lymphocytes than poly I:C-activated CD1c+ DCs. Importantly, CD141+ DCs, but not CD1c+ DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141+ DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8alpha+ DC subset. The data demonstrate a role for CD141+ DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, South Brisbane, Queensland 4101, Australia.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Jongbloed
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Kassianos
authors.forename: Kylie J
authors.initials: KJ
authors.lastname: McDonald
authors.forename: Georgina J
authors.initials: GJ
authors.lastname: Clark
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Ju
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Angel
authors.forename: Chun-Jen J
authors.initials: CJ
authors.lastname: Chen
authors.forename: P Rod
authors.initials: PR
authors.lastname: Dunbar
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wadley
authors.forename: Varinder
authors.initials: V
authors.lastname: Jeet
authors.forename: Annelie J E
authors.initials: AJ
authors.lastname: Vulink
authors.forename: Derek N J
authors.initials: DN
authors.lastname: Hart
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Radford
mesh_terms: D000941:Antigens / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D045142:Cross-Priming / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D022423:Myeloid Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D009336:Necrosis / Q000276:immunology* / Q000473:pathology; D010750:Phosphoproteins / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018180:Thrombomodulin / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000941:Antigens; D018949:Antigens, CD1; D000954:Antigens, Surface; D010750:Phosphoproteins; D011994:Recombinant Proteins; C546931:THBD protein, human; C495344:TLR3 protein, human; D018180:Thrombomodulin; D051196:Toll-Like Receptor 3; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D018664:Interleukin-12; D016899:Interferon-beta; D011070:Poly I-C