Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs.
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.
Ferlazzo
Guido
G
Laboratory of Viral Immunobiology, The Rockefeller University, New York, NY 10021, USA. ferlazg@rockefeller.edu
Pack
Maggi
M
Thomas
Dolca
D
Paludan
Casper
C
Schmid
Dorothee
D
Strowig
Till
T
Bougras
Gwenola
G
Muller
William A
WA
Moretta
Lorenzo
L
Münz
Christian
C
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
D019002:CD56 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D017452:Receptors, IgG; D018664:Interleukin-12; D007371:Interferon-gamma