Trophoblast cell line resistance to NK lysis mainly involves an HLA class I-independent mechanism

The lack of classical HLA molecules on trophoblast prevents allorecognition by maternal T lymphocytes, but poses the problem of susceptibility to NK l ysis, Expression of the nonclassical class I molecule, HLA-G, on cytotropho blast may provide the protective effect. However, the class I-negative sync ytiotrophoblast escapes NK lysis by maternal PBL. In addition, while HLA-G- expressing transfectants of LCL.721.221 cells are protected from lymphokine -activated killer lysis, extravillous cytotrophoblast cells and KLA-G-expre ssing choriocarcinoma cells (CC) are not. The aim of this work was therefor e to clarify the role of HLA class I expression on trophoblast cell resista nce to NK lysis and on their susceptibility to lymphokine-activated killer lysis. Our results showed that both JAR (HLA class I-negative) and JEG-3 (H LA-G- and HLA-Cw4-positive) cells were resistant to NK lysis by PBL and wer e equally lysed by IL-2-stimulated PBL isolated from a given donor. In agre ement, dean-regulating KLA class I expression on JEG-3 cells by acid treatm ent, masking these molecules or the putative HLA-G (or HLA-E) receptor CD94 /NKG2 and the CD158a/p58.1 NKR with mAbs, and inducing self class I molecul e expression on JAR cells did not affect NK or LAK lysis of CC. These resul ts demonstrate that the resistance of CC to NK lysis mainly involves an HLA class I-independent mechanism(s), In addition, we show that the expression of a classical class I target molecule (HLA-B7) on JAR cells is insufficie nt to induce lysis by allospecific polyclonal CTL.