title: Cutting edge: Priming of NK cells by IL-18.
abstract: 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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Institut National de la Santé et de la Recherche Médicale Unité, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6102, Marseille, France
authors.forename: Julie
authors.initials: J
authors.lastname: Chaix
authors.forename: Marlowe S
authors.initials: MS
authors.lastname: Tessmer
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fuséri
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.forename: Lena
authors.initials: L
authors.lastname: Alexopoulou
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
authors.forename: Laurent
authors.initials: L
authors.lastname: Brossay
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020382:Interleukin-18; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D018664:Interleukin-12; D007371:Interferon-gamma