Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation.
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-gamma and tumor-necrosis factor-alpha 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-gamma and tumor-necrosis factor-alpha, 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.
Chen
Yong
Y
Department of Hepatobliliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Liu
Haizhong
H
Liu
Zuojin
Z
Liang
Shaoyong
S
Chen
Jie
J
Long
Feiwu
F
Peng
Yong
Y
Yan
Lünan
L
Gong
Jianping
J
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis; D015153:Blotting, Western; D015536:Down-Regulation; D006084:Graft Rejection / Q000517:prevention & control*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000097:blood; D008055:Lipids; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008853:Microscopy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000945:Antigens, Differentiation, T-Lymphocyte; C556695:Icos protein, rat; D007202:Indicators and Reagents; D060889:Inducible T-Cell Co-Stimulator Protein; D008055:Lipids; C086724:Lipofectamine; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma