摘要
AIM: To investigate the role of adenovirus-mediated CTLA4Ig gene therapy in inhibiting the infiltration of macrophages and CD8+T cells and cell apoptosis after liver transplantation. METHODS: The rat orthotopic liver transplantation model was applied. The rats were divided into three groups: group I: rejection control (SD-to-Wistar); group Ⅱ: acute rejection treated with intramuscular injection of CsA 3.0 mg/(kg·d) for 12 d (SD-to-Wistar+CsA); groupⅢ: injection of 1×10^9 PFU adenovirus-mediated CTLA41g gene liquor in dorsal vein of penis 7 d before liver transplantation (SD-to-Wistar+CTLA4Ig). Immunohistochemistry and transferase-mediated dUTP nick-end labeling (TUNEL )were used to analyze the expression of CTLA4Ig gene in liver, infiltration of macrophages and CD8+T cells, cell apoptosis in grafts at different time-points after liver transplantation. Histopathological examination was done. RESULTS: CTLA4Ig gene expression was positive in liver on d 7 after administering adenovirus-mediated CTLA4Ig gene via vein, and remained positive until day 60 after liver transplantation. Infiltration of macrophages and CD8+T cells in CTLA4Ig-treated group was less than in rejection control group and CsA-treated group. The apoptotic index of rejection group on d 3, 5, and 7 were significantly higher than that of CTLA4Ig-treated group. A good correlation was found between severity of rejection reaction and infiltration of immune activator cells or cell apoptotic index in grafts. CONCLUSION: CTEA4Ig gene is constantly expressed in liver and plays an important role in inducing immune tolerance,
AIM: To investigate the role of adenovirus-mediated CTLA4Ig gene therapy in inhibiting the infiltration of macrophages and CD8+T cells and cell apoptosis after liver transplantation. METHODS: The rat orthotopic liver transplantation model was applied. The rats were divided into three groups: group I: rejection control (SD-to-Wistar); group II: acute rejection treated with intramuscular injection of CsA 3.0 mg/(kg·d) for 12 d (SD-to-Wistar+CsA); groupIII: injection of 1×109 PFU adenovirus-mediated CTLA4Ig gene liquor in dorsal vein of penis 7 d before liver transplantation (SD-to-Wistar+CTLA4Ig). Immunohistochemistry and transferase-mediated dUTP nick-end labeling (TUNEL) were used to analyze the expression of CTLA4Ig gene in liver, infiltration of macrophages and CD8+T cells, cell apoptosis in grafts at different time-points after liver transplantation. Histopathological examination was done. RESULTS: CTLA4Ig gene expression was positive in liver on d 7 after administering adenovirus-mediated CTLA4Ig gene via vein, and remained positive until day 60 after liver transplantation. Infiltration of macrophages and CD8+T cells in CTLA4Ig-treated group was less than in rejection control group and CsA-treated group. The apoptotic index of rejection group on d 3, 5, and 7 were significantly higher than that of CTLA4Ig-treated group. A good correlation was found between severity of rejection reaction and infiltration of immune activator cells or cell apoptotic index in grafts. CONCLUSION: CTLA4Ig gene is constantly expressed in liver and plays an important role in inducing immune tolerance.
作者
Guo-Ping Jiang, Zhen-Hua Hu, Shu-Sen Zheng, Chang-Ku Jia, Ai-Bin Zhang, Wei-Lin Wang, Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China
基金
Supported by Natural Science Foundation of Zhejiang Province,No. 300503Project of Education Administration of Zhejiang Province, No. 20020792
