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 ce...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-11, Vol.101 (47), p.16606-16611
Main Authors: Ferlazzo, Guido, Pack, Maggi, Thomas, Dolca, Paludan, Casper, Schmid, Dorothee, Strowig, Till, Bougras, Gwenola, Muller, William A., Moretta, Lorenzo, Münz, Christian, Steinman, Ralph M.
Format: Article
Language:English
Subjects:
Biological Sciences
Blood
CD56 Antigen - metabolism
Cell Communication - immunology
Cell Division
Cell lines
Cultured cells
Cytokines
Dendritic Cells - immunology
Humans
Immunity, Innate
Immunology
In Vitro Techniques
Interferon-gamma - biosynthesis
Interleukin-12 - antagonists & inhibitors
Interleukin-12 - physiology
Interleukin-15 - physiology
Interleukin-2 - antagonists & inhibitors
Interleukin-2 - physiology
Killer Cells, Natural - cytology
Killer Cells, Natural - immunology
L cells
Lymph nodes
Lymphatic system
Lymphocyte Activation
Lymphoid Tissue - cytology
Lymphoid Tissue - immunology
Natural killer cells
Receptors, IgG - metabolism
Secretion
Spleen
T lymphocytes
T-Lymphocytes - cytology
T-Lymphocytes - immunology
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Summary: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 CD56brightCD16-NK cell subset, which is enriched in secondary lymphoid tissues. Blocking of IL-12 abolished DC-induced IFN-γ 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0407522101