HLA-G inhibits xenogenetic cytotoxicity mediated by human NK cells and T lymphocytes against PECs

The worldwide shortage in the supply of human do-nor organs is becoming more and more pronounced. Xenotransplantation may probably give the hope to over-come the problem ultimately. Because it has a great pros-pect of clinical application, xenotransplantation has drawn great attention1]. The pig appears to be an ideal source for human transplantation. But the xenograft has to face the challenge of three severe rejections (the hyperacute rejec-tion, the delayed xenograft rejection and acute ce…

HLA-G inhibits xenogenetic cytotoxicity mediated by human NK cells and T lymphocytes against PECs

In order to investigate whether the non-classi-cal HLA-G classⅠmolecule protects the porcine endothelial cells (PECs) from the lysis mediated by human immune cells in pig to human discordant xenotransplantation, we have cloned HLA-G cDNA from a human placenta by RT-PCR. Mammalian expression vector, pEFG-neo, was constructed by insertion of HLA-G cDNA in pEF-neo. We obtained efficiently expressed PECs by stable transfection. Cytotoxicity assay showed that overexpression of HLA-G on PECs was sufficient to inhibit human NK-92 cell lysis. The level of lysis was equal to or less than that of the lysis of human umbilical vein endothelial cells mediated by human NK-92 cells. It also indicated that HLA-G inhibited the lysis of PECs mediated by xeno-antigen specific T lymphocytes. The reduction of lysis ranged between 59.1% and 88.9%. These findings suggest that the transgenic approach to overexpress HLA-G is believed to be a new immunotherapy in overcoming the immune rejections in xenotransplantion, including delayed xenograft rejection and cell-mediated rejection.