NK cells provide helper signal for CD8+ T cells by inducing the expression of membrane-bound IL-15 on DCs

Int Immunol. 2009 May;21(5):599-606. doi: 10.1093/intimm/dxp029. Epub 2009 Mar 26.

Abstract

NK cell recognition of cells that do not express or express low amounts of MHC class I molecules results not only in direct killing of target cells but also in the generation of specific T cell responses consequent to the induction of dendritic cell (DC) activation. While IL-12 production by NK cell-activated DCs is generally thought to play a critical role, a similar DC-mediated NK cell help has been reported also in IL-12-knockout mice. Here, we show that human NK cells can induce on DC surface membrane, via IFN-gamma secretion, the expression of high levels of IL-15. Remarkably, we show that DC expression of this membrane-bound form of IL-15, which is only partially associated with IL-15R molecules, is essential to promote specific CD8(+) T lymphocyte response in the absence of DC-derived IL-12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Interferon-gamma / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-15 / immunology*
  • Interleukin-15 / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Receptors, Interleukin-15 / immunology*
  • Receptors, Interleukin-15 / metabolism
  • Signal Transduction / immunology

Substances

  • IL15RA protein, human
  • Interleukin-15
  • Receptors, Interleukin-15
  • Interferon-gamma