alpha-Galactosylceramide-activated V alpha 14 natural killer T cells mediate protection against murine malaria

Natural killer T (NKT) cells are a unique population of lymphocytes that co express a semiinvariant T cell and natural killer cell receptors, which are particularly abundant in the liver. To investigate the possible effect of these cells on the development of the liver stages of malaria parasites, a glycolipid. alpha-galactosylceramide (alpha-GalCer), known to selectively a ctivate V alpha 14 NKT cells in the context of CD1d molecules, was administ ered to sporozoite-inoculated mice. The administration of alpha-GalCer resu lted in rapid, strong antimalaria activity, inhibiting the development of t he intrahepatocytic stages of the rodent malaria parasites Plasmodium yoeli i and Plasmodium berghei. The antimalaria activity mediated by alpha-GalCer is stage-specific, since the course of blood-stage-induced infection was n ot inhibited by administration of this glycolipid. Furthermore, it was dete rmined that IFN-gamma is essential for the antimalaria activity mediated by the glycolipid. Taken together, our results provide the clear evidence tha t NKT cells can mediate protection against an intracellular microbial infec tion.