Down-regulation of HLA-G boosted natural killer cell-mediated cytolysis in JEG-3 cells cultured in vitro.

OBJECTIVE

To determine how decidual natural killer (NK) cells interact with fetal trophoblasts in vitro.

DESIGN

Prospective study.

SETTING

University hospitals and IVF units.

PATIENT(S): Not applicable.

INTERVENTION(S): Not applicable.

MAIN OUTCOME MEASURE(S): An adenovirus vector containing small interfering RNA (siRNA) specifically targeting the human lymphocyte antigen-G (HLA-G) gene was constructed and applied to diminish HLA-G mRNA expression. The steady-state levels of HLA-G messenger RNA (mRNA) were then checked by reverse transcriptase-polymerase chain reaction (RT-PCR) and protein levels by Western blot analysis. The NK-mediated cell cytotoxicity in the siRNA treated cells was studied by application of a nonradioactive cytotoxicity assay.

RESULT(S): Steady-state levels of HLA-G mRNA and protein were significantly diminished by the targeting siRNA. In cells where HLA-G expression was thus reduced, a significant increase in NK cell-mediated lysis occurred.

CONCLUSION(S): These results indicate that the recombinant adenoviral vectors used were efficient tools for studying HLA-G function. More important, this study reveals an important immunoprotective function for HLA-G in controlling NK cell-mediated lysis of trophoblasts, cells whose role in mediating normal pregnancy is important.