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Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation
Authors:Yong Chen PhD  Haizhong Liu MD  Zuojin Liu PhD  Shaoyong Liang PhD  Jie Chen MD  Feiwu Long MD  Yong Peng PhD  Lünan Yan PhD  Jianping Gong PhD  
Institution:aDepartment of Hepatobliliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China;bLiver Transplantation Center, West China Hospital, Sichuan University, Chendu, China
Abstract:

Background

The role of inducible costimulator (ICOS) in transplantation immunity remains unclear.

Methods

A Lewis-to-Brown-Norway (BN) rat liver transplant model was used to explore the effect of ICOS blockade by small interference RNA. Recipient survival rate, number of CD25/ICOS-positive cells, ICOS mRNA and protein levels, and interferon-γ and tumor-necrosis factor-α levels were determined.

Results

Recipient survival was significantly prolonged in rats treated with RNA interference. On day 7 after transplantation, there was a diminished frequency of CD25/ICOS-positive cells and an increased frequency of apoptotic T cells. Furthermore, we found that ICOS blockade could inhibit mRNA and protein expression of ICOS, decrease plasma levels of interferon-γ and tumor-necrosis factor-α, suppress cell infiltration into grafts, and promote tolerance in the interference group.

Conclusions

Our data demonstrate that RNA interference is a potent tool to down-modulate ICOS expression and protect allografts from acute rejection.
Keywords:Acute rejection  Inducible costimulator  Live transplantation  RNA interference  T lymphocyte
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