Soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8

The nonpolymorphic soluble HLA-G1 (sHLA-G1) isoform has been reported to be secreted by trophoblast cells at the materno fetal interface, suggesting that it may act as immunomodulator during pregnancy. In this paper, we report that affinity-purified beta(2)-microglobulin-associated sHLA-G1 triggered apoptosis in activated, but not resting CD8(+) peripheral blood cells, We demonstrate by Western blotting that sHLA-G1 enhanced CD95 ligand expression in activated CD8+ cells. Cytotoxicity was inhibited by preincubation of the cells with a CD95 antagonist mAb (ZB4) or a soluble recombinant CD95-Fc, indicating that apoptosis is mediated through the Cn95/CD95 ligand pathway, Finally, we show that such sHLA-G1-induced apoptosis depends on the interaction with CDS molecules, with cell death being blocked by various CD8 mAbs.