title: CD34-derived dendritic cells transfected ex vivo with HIV-Gag mRNA induce polyfunctional T-cell responses in nonhuman primates.
abstract: The pivotal role of DCs in initiating immune responses led to their use as vaccine vectors. However, the relationship between DC subsets involved in antigen presentation and the type of elicited immune responses underlined the need for the characterization of the DCs generated in vitro. The phenotypes of tissue-derived APCs from a cynomolgus macaque model for human vaccine development were compared with ex vivo-derived DCs. Monocyte/macrophages predominated in bone marrow (BM) and blood. Myeloid DCs (mDCs) were present in all tested tissues and were more highly represented than plasmacytoid DCs (pDCs). As in human skin, Langerhans cells (LCs) resided exclusively in the macaque epidermis, expressing CD11c, high levels of CD1a and langerin (CD207). Most DC subsets were endowed with tissue-specific combinations of PRRs. DCs generated from CD34(+)  BM cells (CD34-DCs) were heterogeneous in phenotype. CD34-DCs shared properties (differentiation and PRR) of dermal and epidermal DCs. After injection into macaques, CD34-DCs expressing HIV-Gag induced Gag-specific CD4(+)  and CD8(+)  T cells producing IFN-γ, TNF-α, MIP-1β, or IL-2. In high responding animals, the numbers of polyfunctional CD8(+)  T cells increased with the number of booster injections. This DC-based vaccine strategy elicited immune responses relevant to the DC subsets generated in vitro.
authors.affiliation: CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, DSV, Fontenay-aux-Roses, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Romain
authors.forename: Ellen
authors.initials: E
authors.lastname: van Gulck
authors.forename: Olivier
authors.initials: O
authors.lastname: Epaulard
authors.forename: Sangkon
authors.initials: S
authors.lastname: Oh
authors.forename: Dapeng
authors.initials: D
authors.lastname: Li
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.forename: Antonio
authors.initials: A
authors.lastname: Cosma
authors.forename: Lucille
authors.initials: L
authors.lastname: Adam
authors.forename: Catherine
authors.initials: C
authors.lastname: Chapon
authors.forename: Biliana
authors.initials: B
authors.lastname: Todorova
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.forename: Frédéric
authors.initials: F
authors.lastname: Martinon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000235:genetics; D001854:Bone Marrow Cells; D039521:CD11c Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008252:Macaca fascicularis / Q000276:immunology; D008264:Macrophages; D008297:Male; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D018949:Antigens, CD1; D018952:Antigens, CD34; D039521:CD11c Antigen; C121916:CD207 protein, human; D007376:Interleukin-2; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma