Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells

C Carnaud, D Lee, O Donnars, SH Park… - The Journal of …, 1999 - journals.aai.org
C Carnaud, D Lee, O Donnars, SH Park, A Beavis, Y Koezuka, A Bendelac
The Journal of Immunology, 1999journals.aai.org
Abstract α-Galactosylceramide (α-GalCer) is a glycolipid with potent antitumor properties
that binds to CD1d molecules and activates mouse Vα14 and human Vα24 NKT cells.
Surprisingly, we found that, as early as 90 min after α-GalCer injection in vivo, NK cells also
displayed considerable signs of activation, including IFN-γ production and CD69 induction.
NK activation was not observed in RAG-or CD1-deficient mice, and it was decreased by
pretreatment with anti-IFN-γ Abs, suggesting that, despite its rapid induction, it was a …
Abstract
α-Galactosylceramide (α-GalCer) is a glycolipid with potent antitumor properties that binds to CD1d molecules and activates mouse Vα14 and human Vα24 NKT cells. Surprisingly, we found that, as early as 90 min after α-GalCer injection in vivo, NK cells also displayed considerable signs of activation, including IFN-γ production and CD69 induction. NK activation was not observed in RAG-or CD1-deficient mice, and it was decreased by pretreatment with anti-IFN-γ Abs, suggesting that, despite its rapid induction, it was a secondary event that depended on IFN-γ 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 α-GalCer result from the sequential recruitment of distinct innate and adaptive effector lymphocytes.
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