Immunization with α-galactosylceramide polarizes CD1-reactive NK T cells towards Th2 cytokine synthesis

Abstract

We have compared the immune responses of mice immunized either with α-galactosylceramide (α-GalCer), capable of eliciting a CD1-metiated stimulation of Vα14+ NK T cells, or with lipoarabinomannan ((LAM), a glycophospholipid derived from mycobacteria which is known to be presented by CD1b in humans. Within 24 h, α-GalCer induces a burst of IFN-1 secretion in vivo, and recall with antigen in vitro leads to the synthesis of IL-4 and IL-10 in addition to IFN-γ. Associated with this in vivo cytokine release is a polyclonal activation of splenic B and T cells. CD1-reactive NK T lymphocytes mediate these events, because none of them are observed in α-GalCer-immunized CD1(-/-) mice. LAM immunization fails to promote similar early responses in vivo. Repeated exposure of mice to α-GalCer induces splenic T cells to secrete IL-4 and IL-10 but dramatically reduced levels of IFN-γ. Such a bias in the cytokine balance triggered, by NK T cells stimulated with multiple doses of α-GalCer suggests that this compound might be useful in the induction of Th2 immune responses and the prevention of chronic inflammatory conditions mediated by Th1 cytokines.