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Cytokine. 2006 Sep;35(5-6):229-34. Epub 2006 Oct 18.

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

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Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, Box 8208, 660 South Euclid Ave., St. Louis, MO 63110, USA.


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 alpha and are stimulated by IL-18 to produce IFNgamma. 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 IFNgamma production.

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