IL-18 acts synergistically with IL-15 in stimulating natural killer cell proliferation

Anthony R. French, Erika B. Holroyd, Liping Yang, Sung Jin Kim, Wayne M. Yokoyama

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Mature natural killer (NK) cells are able to vigorously proliferate in response to infectious stimuli such as viral infections. The factors driving NK cell proliferation under these circumstances are only beginning to be characterized. NK cells constitutively express interleukin-18 receptor α and are stimulated by IL-18 to produce IFNγ. Although IL-18 alone is not sufficient to drive NK cell proliferation, we demonstrate that IL-18 is able to act synergistically with IL-15 in stimulating in vitro NK cell proliferation. Furthermore using a NK cell line, we show that this effect occurs through direct stimulation of NK cells by IL-18 rather than through a secondary signal generated by an intermediary cell type. This raises the possibility that IL-18 may act synergistically with IL-15 in driving pathogen-induced NK cell proliferation in addition to its contribution in enhancing IL-12 stimulation of NK cell IFNγ production.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
Issue number5-6
StatePublished - Sep 2006
Externally publishedYes


  • IL-15
  • IL-18
  • NK cells
  • Proliferation

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy


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