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(+). Expansion of these cells was not observed in alpha-GalCer-liposome-treated mice deficient in IL-10 or iNKT cells. MHC and co-stimulatory molecules were down-regulated in CD11c(low)CD180(+) cells compared with conventional dendritic cells (cDCs), suggesting that the former possess characteristics of immature DCs. Meanwhile, the CD11c(low)CD49b(+) cells expressed IL-10 and Ctla4, and possessed greater lytic activity than resting NK cells. These observations suggest that both immature DCs (CD11c(low)CD180(+)) and cytotoxic cells (CD11c(low)CD49b(+)) might be expanded by alpha-GalCer-activated iNKT cells and could therefore be involved in immune tolerance.
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