Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions

J Immunol. 2008 Jun 15;180(12):7887-97. doi: 10.4049/jimmunol.180.12.7887.


IFN-producing killer dendritic cells (IKDC) were initially described as B220(+)CD11c(+)CD3(-)NK1.1(+) tumor-infiltrating cells that mediated part of the antitumor effects of the combination therapy with imatinib mesylate and IL-2. In this study, we show their functional dependency on IL-15 during homeostasis and inflammatory processes. Trans-presentation of IL-15 by IL-15Ralpha allows dramatic expansion of IKDC in vitro and in vivo, licenses IKDC for TRAIL-dependent killing and endows IKDC with immunizing potential, all three biological attributes not shared by B220(-)NK cells. However, IL-15 down-regulates the capacity of IKDC to induce MHC class I- or II-restricted T cell activation in vitro. Trans-presentation of IL-15 by IL-15Ralpha allows IKDC to respond to TLR3 and TLR4 ligands for the production of CCL2, a chemokine that is critical for IKDC trafficking into tumor beds (as described recently). We conclude that IKDC represent a unique subset of innate effectors functionally distinguishable from conventional NK cells in their ability to promptly respond to IL-15-driven inflammatory processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Separation
  • CpG Islands / immunology
  • Cross-Priming / immunology*
  • Dendritic Cells / classification*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Homeostasis / immunology
  • Immunophenotyping
  • Interferons / biosynthesis*
  • Interleukin-15 / deficiency
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology
  • Interleukin-15 / metabolism*
  • Interleukin-15 Receptor alpha Subunit / physiology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic


  • Interleukin-15
  • Interleukin-15 Receptor alpha Subunit
  • Interferons