Pathogenesis of delayed xenograft rejection in pig-to-rhesus monkey cardiac transplantations / 中国免疫学杂志

ABSTRACT

Objective:To investigate the pahtogengesis and pathology of delayed xenograft rejection (DXR) after pig to rhesus monkey heart xenotransplantation.Methods:Heterotopic xenogeneic heart transplantation in the abdominal cavity was performed using piglet as donors.4 monkeys were used as recipients.Complete complement depletion was achieve in the recipients treated with repetitive doses of a high activity cobra venom factor (Y CVF).The recipients were immunosuppressed with a combination of cyclosporine A,cyclophosphamide and steroids.Sera were analyzed for C3,C4 levels and complement activity and anti pig endotheliocyte xenoantibody.The graft were examined histopathologically and immunohistochemically for C3,C4,C5b 9,IgM,IgG,necrosis factor alpha (TNF alpha),intercellular adhesion molecule 1 (ICAM 1),CD57 (NK cells),CD68 (macrophages),CD4 and CD8.Results:The xenografts survived 8,10,13,13 days respectively and all grafts occoured DXR.Venular thrombosis was outstanding feature within DXR xenografts,complicated with interstitial edma,local hemorrhage and myocardial necrosis,with mild to moderate cellular infiltration.The serum C3 levels and complement activity almost decreased to 0 from the day of transplantation due to Y CVF,the C4 level began to decrease 2 4 days before the cardic xenografts losing their function.The anti pig endotheliocyte xenoantibody also decreased after transplantation,and slightly increased during DXR,all rejected xenografts showed C3,C4,C5b 9,IgG and IgM deposits in different degree.Large numbers of macrophages (50% of total leukocytes) were found infiltrating the entire xenograft,a few natural killer cells (8%～10%),some of CD4+T cells (15%) and CD8+T cells (25%) were detcted also,up regulation of ICAM 1 on the graft endothelial cells and TNF alpha in the interstitial were demonstrated in the rejected heart.Conclusion:Both Humor and cell mediated immunologic reaction may play an important role in pahtogengesis of DXR. [