CTLA4-Ig Fusion Protein Induces Immunotolerance Otorthotopic Liver Transplantation In Rhesus Monkeys

[Objectives] The objectives of the study were to explore the role of blocking B7/CD28 costimulation pathway with CTLA4-Ig Fusion protein in inducing tolerance after liver transplantation. Its relative mechanism was discussed too. Orthotopic liver allograft models of rhesus monkeys were employed in this study. The effect of CTLA4-Ig fusion protein on the function of orthotopic liver allograft was also studied in this research.[Materials and Methods] Orthotopic liver transplantation models were Established using rhesus monkeys. 5 cases LT of rhesus monkeys were operated in blank group of control and group of CTLA4-Ig fusion protein each other. General situation and survival of each group were observed. Blood samples were harvested for detecting of IL-2, IL-10 and TNF-αby ELISA, and liver functions were harvested too. Morphologic changes of graft and severity of rejection and AI in the liver cells of rhesus monkeys were assessed last.[Results]①The average survival of blank group of control was 5.56 days. In comparison to it, the average survival of group of CTLA4-Ig fusion protein was 14. 98 days which were statistically prolonged (P＜0. 05).②ALT,AST,TBIL in the liver functions of rhesus monkeys were highly increased in blank group of control, and ALB decreased obviously. While ALT,AST,TBIL and ALB were maintained normal level in group of CTLA4-Ig fusion protein.③Expression of cytokines IL-2 and TNF-αwere highly expressed in blank group of control. While expression cytokines of IL-10 in group of CTLA4-Ig fusion protein was higher than that of blank group of control.④The severity of rejection reaction after day 3 was weaker in group of CTLA4-Ig fusion protein than that of blank group of control in Histological assessment.⑤AI in the liver cells of rhesus monkeys were highly increased in blank group of control compared with that in group of CTLA4-Ig fusion protein.[Conclusions]①CTLA4-Ig fusion protein therapy can induce the switch of cytokine model from Th1 type to Th2 type in grafts, which can induce immunotolerance and prolong the survival of recipients.②CTLA4-Ig fusion protein can block delivering of costimulation pathway via binding to B7 molecule expressed in surface of cells. It plays an important role in inducing immunotolerance.③The half-life of CTLA4-Ig fusion protein is short. But it still can play a determinate role in inducing immunotolerance of Liver transplantation in rhesus monkeys.④The increasing of cytokines IL-2 and TNF-αor the decreasing of cytokines IL-10 may be one of the indexes in monitoring immunotolerance of transplantation in laboratory.