Adenovirus mediated CTLA4Ig gene inhibits infiltration of immune cells and cell apoptosis in rats after liver transplantation.
OBJECTIVE
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 x d) for 12 d (SD-to-Wistar+CsA); groupIII: injection of 1 x 10(9) 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.


CONCLUSIONS
CTLA4Ig gene is constantly expressed in liver and plays an important role in inducing immune tolerance.
Jiang
Guo-Ping
GP
Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. jiangguoping@hotmail.com
Hu
Zhen-Hua
ZH
Zheng
Shu-Sen
SS
Jia
Chang-Ku
CK
Zhang
Ai-Bin
AB
Wang
Wei-Lin
WL
D000069594:Abatacept; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015316:Genetic Therapy; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018796:Immunoconjugates / Q000235:genetics*; D007167:Immunotherapy; D008099:Liver / Q000276:immunology / Q000473:pathology; D016031:Liver Transplantation / Q000401:mortality; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016019:Survival Analysis
D018796:Immunoconjugates; D000069594:Abatacept
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