IDO-Competent-DCs Induced by IFN-γ Attenuate Acute Rejection in rat Liver Transplantation

We established a stable rat model of liver transplantation using Sprague-Dawley rats and Wistar rats in order to investigate the role of the IDO gene in acute rejection after rat liver transplantation. IDO gene expression and IDO enzyme activity were quantified in liver syngeneic grafts and allografts using microdialysis-HPLC. Liver allografts were evaluated for IDO expression by histopathology. We measured liver function-related biomarkers in liver allografts which were re-infused with untreated or IFN-gamma-treated dendritic cells (DCs). We found a significant increase in IDO gene expression and IDO enzyme activity in liver allografts compared the sham and syngeneic graft groups. There was a significant correlation between the number of IDO-positive cells and severity of acute rejection. IDO gene expression and enzyme activity was upregulated in the IFN-gamma-treated DC group within 7 days after transplantation compared to the untreated DC group and survival rates were significantly improved. Our results suggested that IDO gene expression correlates with the severity of acute rejection and that IFN-gamma-induced IDO-positive DCs may attenuate acute rejection and catalyze local tryptophan metabolism via IDO enzyme expression, leading to immune tolerance after liver transplantation.