title: Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs.
abstract: Dendritic cells (DCs) are known to induce the growth and function of natural killer (NK) cells. Here, we address the capacity of DCs to interact with NK cells in human lymphoid organs and identify the role of specific DC-derived cytokines. We demonstrate that DCs colocalize with NK cells in the T cell areas of lymph nodes. In culture, DCs from either blood or spleen primarily stimulate the CD56(bright)CD16- NK cell subset, which is enriched in secondary lymphoid tissues. Blocking of IL-12 abolished DC-induced IFN-gamma secretion by NK cells, whereas membrane-bound IL-15 on DCs was essential for NK cell proliferation and survival. Maturation by CD40 ligation promoted the highest IL-15 surface presentation on DCs and led to the strongest NK cell proliferation induced by DCs. These results identify secondary lymphoid organs as a potential DC/NK cell interaction site and identify the distinct roles for DC-derived IL-12 and IL-15 in NK cell activation.
authors.affiliation: Laboratory of Viral Immunobiology, The Rockefeller University, New York, NY 10021, USA. ferlazg@rockefeller.edu
authors.forename: Guido
authors.initials: G
authors.lastname: Ferlazzo
authors.forename: Maggi
authors.initials: M
authors.lastname: Pack
authors.forename: Dolca
authors.initials: D
authors.lastname: Thomas
authors.forename: Casper
authors.initials: C
authors.lastname: Paludan
authors.forename: Dorothee
authors.initials: D
authors.lastname: Schmid
authors.forename: Till
authors.initials: T
authors.lastname: Strowig
authors.forename: Gwenola
authors.initials: G
authors.lastname: Bougras
authors.forename: William A
authors.initials: WA
authors.lastname: Muller
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D019002:CD56 Antigen / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000502:physiology*; D019409:Interleukin-15 / Q000502:physiology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D019002:CD56 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D017452:Receptors, IgG; D018664:Interleukin-12; D007371:Interferon-gamma