Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs

Guido Ferlazzo*, Maggi Pack, Dolca Thomas, Casper Paludan, Dorothee Schmid, Till Strowig, Gwenola Bougras, William A. Muller, Lorenzo Moretta, Christian Münz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

428 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)16606-16611
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number47
DOIs
StatePublished - Nov 23 2004

Keywords

  • IFN-γ secretion
  • Lymph node
  • Proliferation
  • Spleen
  • Survival

ASJC Scopus subject areas

  • General

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