Immunopathology of an hDAF transgenic pig model liver xenotransplant into a primate

• Published in: Transplantation proceedings 2003-08, Vol.35 (5), p.2041-2042
• Main Authors: Sanchez, A, Ramirez, P, Pino, G, Chavez, R, Majado, M, Munitiz, V, Muñoz, A, Palenciano, C.G, Yelamos, J, Rodriguez-Gago, M, Pons, J.A, Parrilla, P
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Antigens, Differentiation - analysis; Biological and medical sciences; CD55 Antigens - genetics; Drug Therapy, Combination; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - prevention & control; Humans; Immunosuppressive Agents - therapeutic use; Liver Transplantation - immunology; Liver Transplantation - pathology; Liver, biliary tract, pancreas, portal circulation, spleen; Medical sciences; Papio; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Swine; Tissue, organ and graft immunology; Transplantation, Heterologous - immunology; Transplantation, Heterologous - pathology
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/S0041-1345(03)00704-8

hDAF transgenic pigs do not display the inherent hyperacute rejection reactions of pig-to-primate xenotransplants. The purpose of this study was to determine the immunopathologic phenomena following an hDAF transgenic pig hepatic orthotopic xenotransplant into a baboon. Donor animals were unmodified pigs (n = 4) and hDAF transgenic pigs (n = 2). Recipient animals were baboons ( Papio anubis). Liver biopsies were immunostained using monoclonal antibodies to C3, C5b-9, IgG, IgM, CD2, CD4, CD8, CD68, CD20, Bric 216, CD31, and fibrin, and polyclonal antibody to C4. hDAF transgenic grafts showed IgG, IgM, and C4 endothelial deposits. However, no fibrin, C3, or C5b9 deposits were observed after reperfusion. hDAF xenografts displayed CD31 staining in the portal spaces, perilobular areas, and at hepatic sinuisoidal levels. The baboon that lived for 4 days displayed either CD4 or CD8 T-cells periportal infiltrate. Future studies will seek to determine the physiologic role of CD31 hepatic sinusoidal expression in transgenic xenotransplants, and will also study the role of T-cell infiltrates in xenograft rejection.