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 grooup 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. [Objectives]The objectives of the study were to explore the role of TGF-β1 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 TGF-β1 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 TGF-β1 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 6.60 days.In comparison to it,the average survival of group of TGF-β1 was 14.90 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 TGF-β1.③Expression of cytokines IL-2 and TNF-αwere highly expressed in blank group of control.While expression cytokines of IL-10 in group of TGF-β1 was higher than that of blank group of control.④The severity of rejection reaction after day 3 was weaker in group of TGF-β1 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 TGF-β1.[Conclusions]①TGF-β1 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.②TGF-β1 plays an important role in inducing immunotolerance via exerting manifold immunol effects.③The half-life of TGF-β1 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.