Porcine aortic endothelial cells transfected with HLA-G are partially protected from xenogeneic human NK cytotoxicity.
In this study we tested whether the expression of HLA-G protects porcine endothelial cells (PEC) from the lysis mediated by human natural killer (NK) cells. Because HLA-E is not present in PEC, this model provides an ideal tool to study the direct role of HLA-G in NK inhibition. Immortalized porcine aortic endothelial cells (PED) were stably transfected with a vector coding for the HLA-G1 protein and surface expression was demonstrated by flow cytometry analysis. Although the adhesion of human NK cells to PED was not compromised by HLA-G, the expression of HLA-G partially protected PED from the lysis mediated by polyclonal NK lines derived from different donors. A decrease of the surface expression of HLA-G on PED corresponded to a loss of the capacity of PED to inhibit NK cytotoxicity, indicating that the surface density of HLA-G molecules must exceed a certain threshold to protect target cells. In summary, these data show that HLA-G, independent from the presence of HLA-E, can only partially and inefficiently protect PED from human NK cell-mediated cytotoxicity. Because ILT-2/LIR-1 expression did not correlate with HLA-G mediated inhibition, we hypothesize that other yet unidentified receptors expressed by peripheral blood NK cells are involved in the recognition of HLA-G.
Forte
P
P
Department of Internal Medicine, Laboratory for Transplantation Immunology, University Hospital Zürich, Zürich, Switzerland.
Matter-Reissmann
U B
UB
Strasser
M
M
Schneider
M K
MK
Seebach
J D
JD
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology; D001011:Aorta / Q000276:immunology; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology*; D005434:Flow Cytometry; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D013552:Swine; D014162:Transfection
D015478:Antigens, Heterophile; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I