Evaluation of circulating CD4⁺CD25⁺ and liver-infiltrating Foxp3⁺ cells in HCV-associated liver disease

In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs). In this study, we analysed theperipheral blood from 30 patients with HCV-associated chronic liver disease and20 healthy controls by flow cytometry for the evaluation of the Treg population[CD4⁺CD25hi forkhead box protein 3 (Foxp3)⁺], as well as the activated/effectorCD4⁺ T cells (CD4⁺CD25low) and IFN-γ-secreting cells. We also analysed liverbiopsies of the patients by immunohistochemical evaluation of Foxp3⁺ cells. Ourresults showed higher proportions of CD4⁺CD25low and IFN-γ⁺ cells in the patientsthan in the controls. By contrast, the proportions of peripheral CD4⁺CD25hi cellsdid not significantly differ. The 11 patients displaying Foxp3⁺ cells in theliver infiltrates showed significantly higher proportions of peripheralCD4⁺CD25low cells. Moreover, we found lower serum transaminase levels in thepatients than in the controls, as shown by Foxp3⁺ immunohistochemistry, although these results were only statistically significant as regards alanine transaminase(ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in theperipheral blood and lower activity of hepatitis. Therefore, liver-infiltratingTregs may play a role in limiting tissue damage and may thus support an effectiveimmune response against HCV.