Cutting edge: murine dendritic cells require IL-15R alpha to prime NK cells

J Immunol. 2004 Sep 15;173(6):3594-8. doi: 10.4049/jimmunol.173.6.3594.

Abstract

NK cells protect hosts against viral pathogens and transformed cells, and dendritic cells (DCs) play important roles in activating NK cells. We now find that murine IL-15Ralpha-deficient DCs fail to support NK cell cytolytic activity and elaboration of IFN-gamma, despite the fact that these DCs express normal levels of costimulatory molecules and IL-12. By contrast, IL-15Ralpha expression on NK cells is entirely dispensable for their activation by DCs. In addition, blockade with anti-IL-15Ralpha and anti-IL-2Rbeta but not anti-IL-2Ralpha-specific Abs prevents NK cell activation by wild-type DCs. Finally, presentation of IL-15 by purified IL-15Ralpha/Fc in trans synergizes with IL-12 to support NK cell priming. These findings suggest that murine DCs require IL-15Ralpha to present IL-15 in trans to NK cells during NK cell priming.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell-Free System / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interleukin-15 / metabolism
  • Interleukin-15 / physiology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / immunology
  • Protein Subunits / metabolism
  • Protein Subunits / physiology*
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / antagonists & inhibitors
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Interleukin-2 / physiology*

Substances

  • Antibodies, Blocking
  • IL15RA protein, human
  • Il15ra protein, mouse
  • Immunosuppressive Agents
  • Interleukin-15
  • Protein Subunits
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2