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
Unidad Trasplante Hepatico, University Hospital Virgen Arrixaca, Murcia, Spain.
Transplant Proc. 2003 Aug;35(5):2041-2. 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.
人衰变加速因子(hDAF)转基因猪不会出现猪到灵长类动物异种移植固有的超急性排斥反应。本研究的目的是确定hDAF转基因猪肝原位异种移植到狒狒体内后的免疫病理现象。
供体动物为未修饰猪(n = 4)和hDAF转基因猪(n = 2)。受体动物为狒狒(埃及狒狒)。肝活检组织用抗C3、C5b - 9、IgG、IgM、CD2、CD4、CD8、CD68、CD20、Bric 216、CD31和纤维蛋白的单克隆抗体,以及抗C4的多克隆抗体进行免疫染色。
hDAF转基因移植物显示IgG、IgM和C4在内皮细胞沉积。然而,再灌注后未观察到纤维蛋白、C3或C5b9沉积。hDAF异种移植物在门静脉间隙、小叶周围区域和肝血窦水平显示CD31染色。存活4天的狒狒在门静脉周围有CD4或CD8 T细胞浸润。
未来的研究将试图确定CD31在肝血窦表达在转基因异种移植中的生理作用,也将研究T细胞浸润在异种移植排斥中的作用。