Imbalance Between Regulatory T Cells And Th17Cells In Liver Transplantation

Part1:Expression and effect of CD4+CD25+Foxp3+regulatory T cells and Th17cells in peripheral blood of patients following liver transplantationObjective To study the clinical significance of CD4+CD25+Foxp3+Treg cells and Th17cells in peripheral blood (PB) of patients following liver transplantation and determine the relationship between levels of Treg/Th17cells in the PB and acute rejection.Methods A prospective study compared Th17cells from76consecutive benign end-stage liver disease patients who underwent orthotopic liver transplantation from2008to2012to those from20age-matched healthy individuals. PB samples were collected at different time points post-transplant within one year. Blood samples and liver biopsy were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+CD25+Foxp3+Treg cells and CD4+IL-17+cells were measured by using flow cytometry. Liver transplant patients were classified into two groups:rejection group contained17patients who had an episode of acute rejection, and the nonrejection group had the remaining59patients with no acute rejection episodes. Percentages of circulating CD4+CD25+Foxp3+Treg cells and CD4+IL-17+cells were compared between the two liver transplant groups and controls.Results Circulating CD4+CD25+FoxP3+T cells were significantly lower in the patients in rejectors group during acute rejection as compared to the patients in non-rejectors group (P<0.01). The frequency of circulating CD4+CD25highFoxP3+T cells was negatively correlated with Rejection Activity Index (RAI)(r=-0.80, P<0.01). Levels of circulating CD4+IL-17+T cells in the rejection group were significantly higher during acute rejection than those of the non-rejection group (P <0.001). Furthermore, the frequency of CD4+IL-17+cells in PB was positively correlated with Rejection Activity Index (r=0.79, P=0.0002).Conclusion:(1) Monitoring peripheral CD4+CD25highFoxP3+T cell levels may be useful in evaluating the immune state and act as a more sensitive marker for acute rejection diagnose in the patients following liver transplantation.(2) These findings suggest circulating Th17cells may be useful as a surrogate marker for predicting acute rejection of liver transplant recipients. Part2:Expression and effect of CD39on regulatory T cells in peripheral blood of patients following liver transplantationObjective To study the clinical significance CD39on regulatory T cells in peripheral blood (PB) of patients following liver transplantation and evaluate the relationship between levels of CD39+Treg cells in the PB and acute rejection.Methods A prospective study compared CD39+Treg cells from76consecutive benign end-stage liver disease patients who underwent orthotopic liver transplantation from2008to2012to those from20age-matched healthy individuals. PB samples were collected at different time points post-transplant within one year. Blood samples and liver biopsy were also collected at the diagnosis of acute rejection. Percentages of CD39within CD4+CD25+T cells, CD73within CD4+CD25+T cells, FoxP3within CD4+CD25+CD39+T cells and CD4+CD25+CD73+T cells were measured by using flow cytometry. Liver transplant patients were classified into two groups:rejection group contained17patients who had an episode of acute rejection, and the nonrejection group had the remaining59patients with no acute rejection episodes. Percentages of CD39within CD4+CD25+T cells, CD73within CD4+CD25+T cells, FoxP3within CD4+CD25+CD39+T cells and CD4+CD25+CD73+T cells were compared between the two liver transplant groups and controls. Results Percentages of CD39within CD4+CD25+cells were significantly lower in the patients in rejectors group during acute rejection as compared to the patients in non-rejectors group (P=0.0002). The Percentages of CD39within CD4+CD25+cells was negatively correlated with Rejection Activity Index (r=-0.86, P<0.0001). The inhibition rate regarding CD4+CD25+CD39+Treg cells in patients with acute rejection were significantly lower than those without rejection (P<0.0001). Percentages of CD39within CD4+CD25+T cells were negatively correlated with percentages of IL-17cells within CD4+T cells (r=-0.74P=0.0007)Conclusion:(1) Percentages of CD39within CD4+CD25+T cells were significantly lower in the patients in rejectors group during acute rejection and were negatively correlated with RAI.(2) The inhibition rate regarding CD4+CD25+CD39+Treg cells in patients with acute rejection were significantly lower than those without rejection.(3) Percentages of CD39within CD4+CD25+T cells were negatively correlated with percentages of IL-17cells within CD4+T cells.