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- W2128861878 abstract "Background Heme oxygenase (HO)-1 protects transplanted organs from ischemia reperfusion injury and immune rejection. This study sought to investigate whether persistent overexpression of HO-1 in donor livers could improve the survival by expanding T regulatory cells in a rat model of orthotopic liver transplantation. Methods Livers of Dark Agouti rats were intraportally perfused with an AAV expression vector encoding rat HO-1 (AAV-HO-1), and then transplanted into Lewis rats. The survival, HO-1 activity, Banff rejection activity index, serum levels of IL-2 and TNF-α, infiltration of CD4+, CD8+, and Treg (CD4+CD25+Foxp3+) cells into donor livers, and expression of Foxp3, TGF-β, and IL-10 were examined. A mixed lymphocyte reaction (MLR) was performed. Results Intraportal delivery of AAV-HO-1 resulted in persistent expression of HO-1 and increased activity of HO-1 in transplanted livers, leading to prolonged survival of recipients. Overexpression of HO-1 reduced the Banff rejection activity index, and production of IL-2 and TNF-α, inhibited infiltration of CD4+ and CD8+ cells, and increased infiltration of Treg cells, into donor livers. The spleens of recipients expressed higher levels of Foxp3, TGF-β, and IL-10 than those of control rats, and the transplanted livers expressed higher levels of Foxp3 and TGF-β. Splenocytes from the tolerant recipients had higher percentages of Treg cells, and responded poorly to the allogeneic donor splenocytes. Conclusions Persistent expression of HO-1 in donor livers by intraportal delivery of AAV-HO-1 improves the survival by expanding Treg cells. HO-1-based therapies, as described herein, promise new strategies to prevent the rejection of liver transplants. Heme oxygenase (HO)-1 protects transplanted organs from ischemia reperfusion injury and immune rejection. This study sought to investigate whether persistent overexpression of HO-1 in donor livers could improve the survival by expanding T regulatory cells in a rat model of orthotopic liver transplantation. Livers of Dark Agouti rats were intraportally perfused with an AAV expression vector encoding rat HO-1 (AAV-HO-1), and then transplanted into Lewis rats. The survival, HO-1 activity, Banff rejection activity index, serum levels of IL-2 and TNF-α, infiltration of CD4+, CD8+, and Treg (CD4+CD25+Foxp3+) cells into donor livers, and expression of Foxp3, TGF-β, and IL-10 were examined. A mixed lymphocyte reaction (MLR) was performed. Intraportal delivery of AAV-HO-1 resulted in persistent expression of HO-1 and increased activity of HO-1 in transplanted livers, leading to prolonged survival of recipients. Overexpression of HO-1 reduced the Banff rejection activity index, and production of IL-2 and TNF-α, inhibited infiltration of CD4+ and CD8+ cells, and increased infiltration of Treg cells, into donor livers. The spleens of recipients expressed higher levels of Foxp3, TGF-β, and IL-10 than those of control rats, and the transplanted livers expressed higher levels of Foxp3 and TGF-β. Splenocytes from the tolerant recipients had higher percentages of Treg cells, and responded poorly to the allogeneic donor splenocytes. Persistent expression of HO-1 in donor livers by intraportal delivery of AAV-HO-1 improves the survival by expanding Treg cells. HO-1-based therapies, as described herein, promise new strategies to prevent the rejection of liver transplants." @default.
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- W2128861878 date "2011-04-01" @default.
- W2128861878 modified "2023-09-26" @default.
- W2128861878 title "Hepatic Overexpression of Heme Oxygenase-1 Improves Liver Allograft Survival by Expanding T Regulatory Cells" @default.
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- W2128861878 doi "https://doi.org/10.1016/j.jss.2010.11.917" @default.
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