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

alpha-Galactosylceramide (alpha-GalCer) is a glycolipid with potent antitum or properties that binds to CD1d molecules and activates mouse V alpha 14 a nd 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 considera ble signs of activation, including IFN-gamma production and CD69 induction. NK activation was not observed in RAG- or CD1-deficient mice. and it was d ecreased by pretreatment with anti-IFN-gamma Abs, suggesting that, despite its rapid induction, it was a secondary event that depended on IFN-gamma re lease by NKT cells, At later time points, B cells and CD8 T cells also bega n to express CD69, These findings identify a high-speed communication netwo rk 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.