title: The differential production of cytokines by human Langerhans cells and dermal CD14(+) DCs controls CTL priming.
abstract: We recently reported that human epidermal Langerhans cells (LCs) are more efficient than dermal CD14(+) DCs at priming naive CD8(+) T cells into potent CTLs. We hypothesized that distinctive dendritic cell (DC) cytokine expression profiles (ie, IL-15 produced by LCs and IL-10 expressed by dermal CD14(+) DCs) might explain the observed functional difference. Blocking IL-15 during CD8(+) T-cell priming reduced T-cell proliferation by ∼ 50%. These IL-15-deprived CD8(+) T cells did not acquire the phenotype of effector memory cells. They secreted less IL-2 and IFN-γ and expressed only low amounts of CD107a, granzymes and perforin, and reduced levels of the antiapoptotic protein Bcl-2. Confocal microscopy analysis showed that IL-15 is localized at the immunologic synapse of LCs and naive CD8(+) T cells. Conversely, blocking IL-10 during cocultures of dermal CD14(+) DCs and naive CD8(+) T cells enhanced the generation of effector CTLs, whereas addition of IL-10 to cultures of LCs and naive CD8(+) T cells inhibited their induction. TGF-β1 that is transcribed by dermal CD14(+) DCs further enhanced the inhibitory effect of IL-10. Thus, the respective production of IL-15 and IL-10 explains the contrasting effects of LCs and dermal CD14(+) DCs on CD8(+) T-cell priming.
authors.affiliation: Baylor Institute for Immunology Research and Inserm U899, Dallas, TX, USA. jacques.banchereau@roche.com
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: LuAnn
authors.initials: L
authors.lastname: Thompson-Snipes
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Blanck
authors.forename: Yanying
authors.initials: Y
authors.lastname: Cao
authors.forename: Sandra
authors.initials: S
authors.lastname: Clayton
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.forename: Eynav
authors.initials: E
authors.lastname: Klechevsky
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D045142:Cross-Priming / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D020405:Dermis / Q000166:cytology*; D006801:Humans; D054992:Immunological Synapses / Q000187:drug effects; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000494:pharmacology; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000494:pharmacology; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D019138:Antibodies, Blocking; D019409:Interleukin-15; D018950:Lipopolysaccharide Receptors; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10