The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes

In vivo administration of NKT cell ligand, alpha-galactosylceramide (alpha- GalCer), caused the activation of NKT cells to induce a strong NK activity and cytokine production by CD1d-restricted mechanisms. Surprisingly, we als o found that alpha-GalCer induced the activation of immunoregulatory cells involved in acquired immunity. Specifically, in vivo administration of alph a-GalCer resulted in the induction of the early activation marker CD69 on C D4(+) T cells, CD8(+) T cells and B cells in addition to macrophages and NK T cells, However, no significant induction of CD69 was observed on cells fr om CD1d- or V(alpha)14 NKT-deficient mice, indicating an essential role for the interaction between NKT cells and CD1d-expressing dendritic cells (DC) in the activation of acquired immunity in response to alpha-GalCer, Indeed , in vivo injection of alpha-GalCer resulted not only in the activation of NKT cells but also in the generation of CD69(+)CD8(+) T cells possessing bo th cytotoxic T lymphocyte (CTL) activity and IFN-gamma-producing ability, T umor-specific CTL generation was also accelerated by alpha-GalCer, The crit ical role of CD40-CD40 ligand (CD40L)-mediated NKT-DC interaction during th e development of CD69(+)CD8(+) CTL by alpha-GalCer was demonstrated by bloc king experiments using anti-CD40L mAb, These findings provide direct eviden ce for a critical role of CD1d-restricted NKT cells and DC in bridging inna te and acquired immunity.