Cutting edge: Priming of NK cells by IL-18.

Julie Chaix (1) , Marlowe S Tessmer (2) , Kasper Hoebe (3) , Nicolas Fuséri (1) , Bernhard Ryffel (4) , Marc Dalod (1) , Lena Alexopoulou (1) , Bruce Beutler (5) , Laurent Brossay (2) , Eric Vivier (1) , Thierry Walzer (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 Department of Molecular Microbiology and Immunology
3 Division of Molecular Immunology
4 IEM - Immunologie et Embryologie Moléculaires
5 Department of Immunology and Microbial Science

Recent evidence suggests that NK cells require priming to display full effector activity. In this study, we demonstrate that IL-18 contributed to this phenomenon. IL-18 signaling-deficient NK cells were found to be unable to secrete IFN-gamma in response to ex vivo stimulation with IL-12. This was not due to a costimulatory role of IL-18, because blocking IL-18 signaling during the ex vivo stimulation with IL-12 did not alter IFN-gamma production by wild-type NK cells. Rather, we demonstrate that IL-18 primes NK cells in vivo to produce IFN-gamma upon subsequent stimulation with IL-12. Importantly, IL-12-induced IFN-gamma transcription by NK cells was comparable in IL-18 signaling-deficient and -sufficient NK cells. This suggests that priming by IL-18 leads to an improved translation of IFN-gamma mRNA. These results reveal a novel type of cooperation between IL-12 and IL-18 that requires the sequential action of these cytokines.

Domaines: Immunologie

Julie Chaix, Marlowe S Tessmer, Kasper Hoebe, Nicolas Fuséri, Bernhard Ryffel, et al.. Cutting edge: Priming of NK cells by IL-18.. Journal of Immunology, 2008, 181 (3), pp.1627-31. ⟨hal-00363717⟩