Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model

• Published in: Scientific reports 2017-08, Vol.7 (1), p.10024-11, Article 10024
• Main Authors: Zhang, Junfang, Xie, Chongwei, Lu, Ying, Zhou, Ming, Qu, Zepeng, Yao, Da, Qiu, Chuanghua, Xu, Jia, Pan, Dengke, Dai, Yifan, Hara, Hidetaka, Cooper, David K. C., Ma, Shanshan, Li, Mingtao, Cai, Zhiming, Mou, Lisha
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/31; 14; 14/34; 42; 42/109; 42/41; 42/47; 45; 45/41; 631/250/1854/2812; 631/250/2152/569/2495; 692/308/575; Animals; Antigens; Antigens - genetics; Antigens - immunology; Aorta; Cells, Cultured; Clonal deletion; Cytotoxicity; Endothelial cells; Endothelial Cells - immunology; Endothelium, Vascular - immunology; Female; Galactosyltransferases - genetics; Galactosyltransferases - immunology; Gene expression; Graft Rejection - genetics; Graft Rejection - immunology; Heterografts - immunology; Humanities and Social Sciences; Humans; Immune response; Immunization; Immunogenicity; Kidney - blood supply; Kidneys; Macaca fascicularis; Microvasculature; multidisciplinary; Science; Science (multidisciplinary); Swine; Transcriptome; Xenografts; Xenotransplantation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-10805-0

When hyperacute rejection is avoided by deletion of Gal expression in the pig, delayed xenograft rejection (DXR) becomes a major immunologic barrier to successful xenotransplantation. This study was to investigate the potential antigens involved in DXR. We isolated primary renal microvascular endothelial cells (RMEC) and aortic endothelial cells (AEC) from a GGTA1/CMAH double-knockout (DKO) pig (and a GGTA1-KO pig) and immunized cynomolgus monkeys with both of these cells. After sensitization, monkey serum antibody binding and cytotoxicity to RMEC was significantly higher than to AEC(p