Cutting edge: Activation of NK T cells by CD1d and alpha-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype

NK T cells recognize glycolipid Ags such as alpha-galactosylceramide (alpha -GalCer) presented by the MHC class I-like molecule CD1d. In this paper we have studied the in vivo effects of alpha-GalCer on the generation of adapt ive immune responses. Treatment of mice with alpha-GalCer resulted in rapid activation of NK T cells and production of the cytokines IL-4 and IFW-gamm a. However, after this initial stimulation, NK T cells became polarized for the production of IL-4, Further, as soon as 6 days after alpha-GalCer inje ction, a marked increase in serum IgE levels was observed. Administration o f alpha-GalCer at the time of priming of mice with protein Ag resulted in t he generation of Ag-specific Th2 cells and a profound increase in the produ ction of IgE, Collectively, these findings indicate that alpha-GalCer may b e useful for modulating immune responses toward a Th2 phenotype during prop hylaxis and therapy.