Production of both IL-27 and IFN-gamma after the treatment with a ligand for invariant NK T cells is responsible for the suppression of Th2 response and allergic inflammation in a mouse experimental asthma model.

Using an allergen-induced airway inflammation model, we show that an injection of alpha-galactosylceramide (alpha-GalCer), a ligand for invariant NK T (iNKT) cells, induced IL-27 and that this process is essential for the attenuation of the Th2 response. After the systemic administration of alpha-GalCer into the mice primed with OVA in alum, Th2 cytokine production of OVA-primed CD4(+) T cells in their lymph nodes, IgG1 and IgE Ab formation, and infiltration of eosinophils in bronchoalveolar lavage after the OVA challenge were suppressed. Systemic administration of rIFN-gamma into OVA-primed mice could not reproduce these effects of alpha-GalCer.

Alpha-galactosylceramide-driven immunotherapy for allergy.

We report here that the delivery of both alpha-galactosylceramide (alphaGalCer), a representative ligand for invariant natural killer T (iNKT) cells, and an antigenic polypeptide to marginal zone B cells induces the differentiation of regulatory cells in vivo, and suppresses the secondary antibody responses in mice. Splenic CD21+ CD23- B cells of mice treated with alphaGalCer-liposomes produce IL-10 when co-cultured with iNKT cells, whereas the cells treated with aqueous alphaGalCer fail to do so. Adoptive transfer of the B cells into syngenic mice leads to the expansion of splenic CD11c(low) CD45RB(high) cells, which convert naive CD4+ T cells from RAG2-deficient DO11.

Characterization of the immature dendritic cells and cytotoxic cells both expanded after activation of invariant NKT cells with alpha-galactosylceramide in vivo.

Invariant natural killer T (iNKT) cells can perform multiple functions characteristic of both innate and acquired immunity. Activation of iNKT cells in vivo by repeated alpha-GalCer injections can induce immune tolerance, but the mechanisms responsible for such immunoregulation remain unclear. We prepared alpha-GalCer-liposomes, a single injection of which into mice resulted in the expansion of splenic CD11c(low)CD45RB(high) cells, which consists of two populations, CD180(+) and CD49b(+).