Regulatory T Cells in Clinical Liver Transplantation

Background: Regulatory T-cells (Tregs) (CD4+CD25+Foxp3+) have a key role in tolerance and may influence allograft outcome. Tregs have been extensively studied in animals however their role in clinical transplantation remains unknown. Aim: Identify and characterize Tregs in the peripheral blood of liver transplant recipients. Methods: We performed a cross-sectional study phenotyping peripheral blood lymphocytes by flow cytometry and correlate these with clinical parameters. Groups examined included: (a) Normal Healthy Controls (n=10); (b) Patients with liver failure on the waiting list (n=15) and (c) Liver Transplant Reicpients (LTR) (n=101). Results: The proportion of CD25+ cells in CD4+ population was shown to be lower in LTR compared with the two controls. The level of CD4+CD25+Foxp3+ T cells (within CD4+ population) was higher in patients with chronic liver disease awaiting transplantation and LTR compared to the normal controls. LTR with a history of pre-transplant malignancy (hepatocellular carcinoma) had significantly higher levels of CD4+CD25+Foxp3+ cells in the CD4+ population compared to patients without pre-transplant malignancy. Treg phenotype correlated with age. An inverse correlation was observed between CD127 and Foxp3 expression in CD4+CD25+ cells. Conclusion: (1) Lower CD4+CD25+ cells in LTR may relate to immunosuppression; (2) Higher levels of CD4+CD25+Foxp3+ cells in LTR and patients with liver disease may contribute to a suppressed immune state; (3) CD4+CD25+Foxp3+ may be a marker of tendency to malignancy. Future studies are required to understand the biological significance of these cells and confirm these findings.