Miscarriage induced by adoptive transfer of dendritic cells and invariant natural killer T cells into mice

Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205(+) dendritic cells (DCs) and NK1.1(+) invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of -galactosylceramide (-GalCer). Here we demonstrate that the adoptive transfer of DEC-205(+) bone marrow-derived DCs cocultured with -GalCer (DEC-205(+) BMDCs-c/w--GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (f) x BALB/c (o)), which was accompanied by the accumulation of activated iNKT cells in the myometrium. Further, the adoptive transfer of NK1.1(+) iNKT cells obtained from B6 mice injected with -GalCer facilitated miscarriages in syngeneic J18((-/-)) (iNKT cell-deficient) mice. These results suggest that DEC-205(+) DCs and NK1.1(+) iNKT cells play crucial roles required for the initiation of fetal loss associated with stimulation by glycolipid antigens and sterile inflammation.