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The Journal of Immunology, 1999, 163: 4647-4650.
Copyright © 1999 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: Cross-Talk Between Cells of the Innate Immune System: NKT Cells Rapidly Activate NK Cells1

Claude Carnaud2,*,{dagger}, Daniel Lee*, Olivier Donnars{dagger}, Se-Ho Park*, Andrew Beavis*, Yasuhiko Koezuka{ddagger} and Albert Bendelac*

* Department of Molecular Biology, Princeton University, Princeton, NJ 08544; {dagger} Institut National de la Santé et de la Recherche Médicale U25, Hopital Necker, Paris, France; and {ddagger} Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd, Gunma, Japan

{alpha}-Galactosylceramide ({alpha}-GalCer) is a glycolipid with potent antitumor properties that binds to CD1d molecules and activates mouse V{alpha}14 and human V{alpha}24 NKT cells. Surprisingly, we found that, as early as 90 min after {alpha}-GalCer injection in vivo, NK cells also displayed considerable signs of activation, including IFN-{gamma} production and CD69 induction. NK activation was not observed in RAG- or CD1-deficient mice, and it was decreased by pretreatment with anti-IFN-{gamma} Abs, suggesting that, despite its rapid induction, it was a secondary event that depended on IFN-{gamma} release by NKT cells. At later time points, B cells and CD8 T cells also began to express CD69. These findings identify a high-speed communication network between the innate and adaptive immune systems in vivo that is initiated upon NKT cell activation. They also suggest that the antitumor effects of {alpha}-GalCer result from the sequential recruitment of distinct innate and adaptive effector lymphocytes.




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