The immunological mechanisms that regulate abortion are largely unknown. He
re, we found that a distinct subset of lymphocytes, V alpha 14 NKT cells ex
pressing an invariant antigen receptor encoded by V alpha 14/J alpha 281 an
d V beta 7 segments, accumulated in the decidua during pregnancy and provok
ed abortion upon stimulation with ar-galactosylceramide (alpha-GalCer), a s
pecific ligand for V alpha 14 NKT cells. The alpha-GalCer-mediated abortion
was not observed in V alpha 14 NKT-, IFN-gamma-, tumor necrosis factor alp
ha-, or perforin-knock-out mice and appeared to be due to the degeneration
of embryonic trophoblasts mediated by the activated V alpha 14 NKT cells wh
ose perforin-dependent killing and production of lFN-gamma and tumor necros
is factor alpha were essential. The possible role of the decidual V alpha 1
4 NKT cells in the pathogenesis of abortion is discussed.