Adenovirus-mediated CTLA4Ig gene inhibits infiltration of immune cells and cell apoptosis in rats after liver transplantation

doi:10.3748/wjg.v11.i7.1065

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Feb 21, 2005 (publication date) through Nov 27, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Feb 21, 2005; 11(7): 1065-1069
Published online Feb 21, 2005. doi: 10.3748/wjg.v11.i7.1065

Adenovirus-mediated CTLA4Ig gene inhibits infiltration of immune cells and cell apoptosis in rats after liver transplantation

Guo-Ping Jiang, Zhen-Hua Hu, Shu-Sen Zheng, Chang-Ku Jia, Ai-Bin Zhang, Wei-Lin Wang

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

Author contributions: All authors contributed equally to the work.

Correspondence to: Dr. Guo-Ping Jiang, 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. jiangguoping@hotmail.com

Telephone: +86-571-87236570 Fax: +86-571-87236570

Received: June 24, 2004
Revised: June 27, 2004
Accepted: August 21, 2004
Published online: February 21, 2005

Abstract

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.

Keywords: Liver transplantation; Adenovirus; CTLA4Ig; Apoptosis