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Effects of combined genes of CTLA4Ig and IDO in post-liver transplantation immune tolerance of rats

Yakun Wu, Zheng Yu, Junhua Gong, Min Li, Yiming Liu, Jianping Gong


Background and rationale for the study. Previous studies showed that CTLA4Ig and indoleamine 2,3-dioxygenase (IDO) genes played regulatory role in organ transplantation but failed to reach satisfactory effects. In this study, we constructed an adenovirus- mediated gene expressing CTLA4Ig–IDO and established rat liver transplantation models. Recipients were randomly divided into four groups of 10 rats each. During the operation, CTLA4Ig, IDO, and CTLA4Ig–IDO genes, as well as a blank plasmid, were infused into different rat groups via portal vein to determine their effects on inducing immune tolerance. Survival rate of recipients, histological changes of graft liver, post-transplantation liver function, and cytokine levels were observed at day 14 after operation. Results. Serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin level (TBIL) in the CTLA4Ig-IDO group were lower than those in the other three groups at 14 days post-transplantation (P < 0.05); mRNA and protein expressions of IL-2 and IFN-γ were higher in the control group, but lower in the CTLA4Ig-IDO group (P < 0.05). By contrast, expressions of IL-4, TGF-b, IL-10, and T lymphocyte apoptosis were higher in the CTLA4Ig-IDO group than those in the other three groups (P < 0.05). The CTLA4Ig-IDO group exhibited mild acute rejection and higher survival rate compared with the other groups (P < 0.05). Conclusion. Compared with using CTLA4Ig or IDO alone, combined transfection of CTLA4Ig-IDO was more effective in inducing immune tolerance after liver transplantation.

Key words. Liver transplantation, Immune tolerance, Combined infusion, CTLA4Ig-IDO, Rat

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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