title: Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses.
abstract: Dendritic cells (DC) have the unique capacities to induce primary T-cell responses. In mice, CD8α(+)DC are specialized to cross-prime CD8(+) T cells and produce interleukin-12 (IL-12) that promotes cytotoxicity. Human BDCA-3(+)DC share several relevant characteristics with CD8α(+)DC, but the capacities of human DC subsets to induce CD8(+) T-cell responses are incompletely understood. Here we compared CD1c(+) myeloid DC (mDC)1, BDCA-3(+)mDC2, and plasmacytoid DC (pDC) in peripheral blood and lymphoid tissues for phenotype, cytokine production, and their capacities to prime cytotoxic T cells. mDC1 were surprisingly the only human DC that secreted high amounts of IL-12p70, but they required combinational Toll-like receptor (TLR) stimulation. mDC2 and pDC produced interferon-λ and interferon-α, respectively. Importantly, mDC1 and mDC2 required different combinations of TLR ligands to cross-present protein antigens to CD8(+) T cells. pDC were inefficient and also expressed lower levels of major histocompatibility complex and co-stimulatory molecules. Nevertheless, all DC induced CD8(+) memory T-cell expansions upon licensing by CD4(+) T cells, and primed naive CD8(+) T cells following appropriate TLR stimulation. However, because mDC1 produced IL-12, they induced the highest levels of cytotoxic molecules. In conclusion, CD1c(+)mDC1 are the relevant source of IL-12 for naive T cells and are fully equipped to cross-prime cytotoxic T-cell responses.
authors.affiliation: National Institute of Molecular Genetics, Via Francesco Sforza 35, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Nizzoli
authors.forename: Jana
authors.initials: J
authors.lastname: Krietsch
authors.forename: Anja
authors.initials: A
authors.lastname: Weick
authors.forename: Svenja
authors.initials: S
authors.lastname: Steinfelder
authors.forename: Federica
authors.initials: F
authors.lastname: Facciotti
authors.forename: Paola
authors.initials: P
authors.lastname: Gruarin
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bianco
authors.forename: Bodo
authors.initials: B
authors.lastname: Steckel
authors.forename: Monica
authors.initials: M
authors.lastname: Moro
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Crosti
authors.forename: Chiara
authors.initials: C
authors.lastname: Romagnani
authors.forename: Katharina
authors.initials: K
authors.lastname: Stölzel
authors.forename: Sara
authors.initials: S
authors.lastname: Torretta
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pignataro
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
authors.forename: Petra
authors.initials: P
authors.lastname: Neddermann
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; C437944:CD1C protein, human; D016207:Cytokines; D006023:Glycoproteins; D016898:Interferon-alpha; D051193:Toll-Like Receptors; D018664:Interleukin-12; D007371:Interferon-gamma