Susceptibility of MHC class I expressing extravillous trophoblast cell lines to killing by natural killer cells

Purified human first trimester extravillous trophoblast (EVT) cell lines HT R-8 and HT-116 were examined for susceptibility to natural killer (NK) cell -mediated lysis. Based upon nucleic acid sequencing of an amplified fragmen t of cDNA, Western blot analysis and immunostaining of fixed and live cells , it was shown that both EVT cell lines expressed HLA-G mRNX and protein wi thin the cytoplasm when cultured on laminin-coated plates. Very weak HLA-G expression was detectable on the cell surface under these conditions. Howev er, strong cell surface expression of a classical MHC class I molecule (mos t likely HLA-C) was exhibited by these EVT cell lines when grown on laminin , as indicated by W6/32 FAGS analysis (Ab recognizing pan MHC class I), and Western immunoblotting with HC10 (Ab recognizing HLA-B/C). When these EVT cells, cultured on laminin, were used as targets for peripheral blood natur al killer (NK) cells in a standard chromium release assay, both HTR-8 and H T-116 cells were lysed by NK cells in a dose-dependent manner. The respecti ve percentage specific lysis at an effector to target (E/T) ratio of 100 wa s 28 +/- 7, acid 48 +/- 14. The choriocarcinoma cell lines JAR and JEG-3 wh ich were respectively MHC class I negative and HLA-G positive were resistan t to NK cell lysis. Thus, there was no clear relationship between the MHC c lass I expression and NK cell resistance or susceptibility among the EVT ce ll lines and choriocarcinoma cells. These findings raise the possibility th at NK cells may take part in the surveillance of the invasive EVT cells dur ing normal placentation. (C) 1999 W. B. Saunders Company Ltd.