Chinese Journal of Tissue Engineering Research ›› 2012, Vol. 16 ›› Issue (53): 9934-9940.doi: 10.3969/j.issn.2095-4344.2012.53.011

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Immune tolerance of rat liver transplantation induced by pre-infusion of RNA interference RelB short hairpin RNA lentiviral modified dendritic cells

Xie Jin-min1, 2, Wang Yan3, Bao Jie4, Ma Yong-ge2, Zou Zhi-hao2, Tang Zeng-jie2, Dong Rui-qiang5, Wen Hao1   

  1. Post-doctoral Station of Clinic Medicine, the First Teaching Hospital of Xinjiang Medical University, Urumqi 830012, Xinjiang Uygur Autonomous Region, China
    2The 23th Hospital of Chinese PLA, Urumqi 830011, Xinjiang Uygur Autonomous Region, China
    3Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
    4Department of Laboratory Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China
    5Medical College of Shihezi University, Shihezi 834407, Xinjiang Uygur Autonomous Region, China
  • Received:2012-03-03 Revised:2012-04-29 Online:2012-12-30 Published:2012-12-30
  • Contact: Wen Hao, Doctor, Professor, Post-doctoral Station of Clinic Medicine, the First Teaching Hospital of Xinjiang Medical University, Urumqi 830012, Xinjiang Uygur Autonomous Region, China Dr.wenhao@163.com
  • About author:Xie Jin-min☆, Doctor, Master’s supervisor, Associate chief physician, Post-doctoral Station of Clinic Medicine, the First Teaching Hospital of Xinjiang Medical University, Urumqi 830012, Xinjiang Uygur Autonomous Region, China; The 23th Hospital of Chinese PLA, Urumqi 830011, Xinjiang Uygur Autonomous Region, China platransplantation@163.com

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Abstract:

BACKGROUND: Homograft rejection is the most important factor that limits the survival of recipients and donor organs fter liver transplantation. Induced specific immune tolerance is a most satisfactory method to release rejection after transplantation.
OBJECTIVE: To explore the possibility of the specific immune tolerance induced by RNA interference RelB dendritic cells pre-infusion after liver transplantation in rats.
METHODS: A stable rat model of acute rejection was established by allograft liver transplantation from DA (RT1a) rats to Lewis (RT11) rats. Before transplantation, the donor and recipient rats were paired and randomly divided into four groups: (1)Control group: the recipient rats were not injected before liver transplantation. (2)RNA interference RelB treatment group: the recipient rats were pre-injected with RNA interference RelB dendritic cells from donor (5×106) via veins at the 7 days before transplantation. (3)Immature dendritic cells group: the recipient rats were pre-injected with immature dendritic cells (5×106) from donor via veins at the 7 days before transplantation. (4)Mature dendritic cells group: the recipient rats were pre-injected with mature dendritic cells (5×106) from donor via veins at the 7 days before transplantation.
RESULTS AND CONCLUSION: Compared with control group, immature dendritic cells group and mature dendritic cells group, the average survival time of graft renal in RNA interference RelB treatment group prolonged significantly (P < 0.01). The content of aspartate aminotransferase and total bilirubin in RNA interference RelB treatment group at 7 days after transplantation were significantly lower that those in the control group, immature dendritic cells group and mature dendritic cells group (P < 0.01), while the content of aspartate aminotransferase and total bilirubin at 14 days after transplantation in RNA interference RelB treatment group and immature dendritic cells group were slightly decreased, and there was significant difference between two groups (P < 0.01). At 7 days after transplantation, compared with RNA interference RelB treatment group, the contents of interferon-γ and interleukin-2 were increased in the control group, immature dendritic cells group and mature dendritic cells group (P < 0.01), while the contents of interleukin-4 and interleukin-10 were decreased (P < 0.01); at 14 days after transplantation, the contents of interferon-γ and interleukin-2 were decreased and the contents of interleukin-4 and interleukin-10 were increased in RNA interference RelB treatment group and immature dendritic cells group, and there was significant difference between two groups (P < 0.01). At 7 days after transplantation, the rejection active index in the control group, immature dendritic cells group and mature dendritic cells group was 8.0-9.0. At 14 days after transplantation, more necrosis of hepatocytes and endotheliocyte and inflammatory cells imbibition in header zone were observed in immature dendritic cells group. The rejection active index in RNA interference RelB treatment group at 7 days after transplantation was 6.0-8.0, and rejection active index was 4.0-5.0 at 14 days after transplantation. Pre-injection of RNA interference RelB dendritic cells may contribute to reduce the degree of graft rejection and prolong the survival time of grafted liver, which related to the regulation and immune-incompetent of T cells.

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