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

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

Resumen

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 adeno-virus-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 infusedinto 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-IDOgroup were lower than those in the other three groups at 14 days post-transplantation (P < 0.05); mRNA and protein expressions ofIL-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 immunetolerance after liver transplantation.

Palabras clave: Liver transplantation immune tolerance combined infusion CTLA4Ig-IDO rat.

2016-10-21   |   224 visitas   |   Evalua este artículo 0 valoraciones

Vol. 15 Núm.5. Septiembre-Octubre 2016 Pags. 729-737 Ann Hepatol 2016; 15(5)