Identification of FoxP3 expression in peripheral blood and liver tissues in Egyptian patients with hepatitis C virus infection

Background FoxP3 constitutive expression is necessary for the suppressive function of regulatory T cells (Tregs). The majority of infected patients with hepatitis C virus (HCV) develop only a weak, narrow, or nonpersistent adaptive response to acute infection. The aim of this study was to investigate the frequency of CD4+FoxP3+ Tregs in peripheral blood and liver biopsy tissues in patients with acute and chronic hepatitis C and their potential association with viral load. Patients and methods The study participants were divided into three groups. Group I comprised 15 recently diagnosed patients with acute hepatitis C. Group II comprised 46 patients with chronic hepatitis C, of whom 21 patients had chronic hepatitis C without hepatic cirrhosis (group IIa) and 25 patients had chronic hepatitis C with hepatic cirrhosis (group IIb). Group III comprised 22 apparently normal individuals and they constituted the control group. Double immunohistochemical analyses were performed on liver biopsy samples for CD4/FoxP3 and CD8/FoxP3. Further, flow cytometric analysis of peripheral blood for CD4, CD8, and FoxP3-positive lymphocytes was carried out. Results Most FoxP3+ cells in the peripheral blood and liver tissues were CD4+ cells, and CD8+FoxP3+ cells were very scare. A considerable number of FoxP3+ cells were observed in the portal tracts and fibrous septa, particularly when lymphoid aggregates were present. They were also observed in parenchymatous areas, where they preferentially localized in necrotic areas. In group I patients there were significant positive correlations between CD4+FoxP3+ cells in peripheral blood and alanine aminotransferase, aspartate aminotransferase, total bilirubin, and viral copies. In chronic hepatitis cases, no correlations were found between CD4+FoxP3+ cells in peripheral blood and liver tissues and other laboratory parameters. Conclusion FoxP3 – Tregs are upregulated in HCV patients, suggesting an important role for Tregs in establishing and/or maintaining HCV persistence. Further studies are needed to examine the role of Tregs in HCV disease pathogenesis and to develop therapeutic approaches to control the balance between Tregs and effector T cells to enhance viral clearance.