Co-effect of HLA-G1 and glycosyltransferases in reducing NK cell-mediated pig endothelial cell lysis.
Natural killer (NK) cells play an important role in xenograft rejection. The aim of this study was to evaluate the co-effect of human leukocyte antigen (HLA)-G1 expression and the remodeling of glycoantigens such as the alpha-Gal epitope, Galalpha1,3Galbeta1,4GlcNAc-R, by the introduction of glycosyltransferase genes related to NK cell-mediated direct cytotoxicity. Human peripheral blood mononuclear cells or an NK-like cell line, YT cells, was used as an effector and pig endothelial cells (PEC) as the target. A PEC transfectant with HLA-G1 was first prepared by the transfection of HLA-G1 and human beta2 microglobulin. Several new transfectants were then established by the transfection of glycosyltransferase to the HLA-G1 transfectant. The effect of HLA-G1 on NK cell-mediated PEC lysis was lower than that by the glycosyltransferases. Therefore, in the case of the co-transfectants except for HLA-G1+alpha2,6sialyltransferase, such as HLA-G1+N-acetylglucosaminyltransferase-III and HLA-G1+alpha1,2fucosyltransferase, the effect of HLA-G1 expression on NK-mediated killing appeared to be accounted for by the transfected glycosyltransferase activities and the reduced alpha-Gal expression on the cell surface. However, these transfectants showed significant reductions in direct NK cell-mediated cytotoxicity, compared with the single HLA-G1 transfectant. The results herein suggest that a combination of HLA-G1 and glycosyltransferases has considerable potential for the downregulation of NK cell-mediated cytolysis.
Miyagawa
Shuji
S
Division of Organ Transplantation, Department of Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan. miyagawa@orgtrp.med.osaka-u.ac.jp
Nakai
Rie
R
Matsunami
Katsuyoshi
K
Kusama
Tamiko
T
Shirakura
Ryota
R
D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology*; D005434:Flow Cytometry; D016695:Glycosyltransferases / Q000235:genetics / Q000276:immunology*; 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
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D016695:Glycosyltransferases