CD4+ and CD8+ Regulatory T Cells (Tregs) are Elevated and Display an Active Phenotype in Patients with Chronic HCV Mono-Infection and HIV/HCV Co-Infection

The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono-infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24 patients with HIV/HCV co-infection and 24 healthy individuals. CD4+ and CD8+ Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4+ and CD8+ Tregs was found in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.76.9) and 1.0% (0.71.2), respectively] compared to HCV mono-infected patients [5.6% (4.26.3), P = 0.01 and 0.5% (0.30.7), P < 0.001, respectively]. Furthermore, HCV mono-infected patients had increased frequencies of Tregs compared with healthy controls (P < 0.05). However, no associations between the frequency of Tregs and fibrosis were found. Furthermore, characterization of CD4+ Tregs using CD45RA demonstrated a higher frequency of activated Tregs in both HCV mono-infected and HIV/HCV co-infected patients compared with healthy controls. Finally, number of intrahepatic Tregs was associated with both peripheral CD8+ Tregs and intrahepatic inflammation. In conclusion, HCV mono-infected patients and particularly HIV/HCV co-infected patients have increased the frequency of CD4+ and CD8+ Tregs compared with healthy controls. Furthermore, CD4+ Tregs in infected patients displayed an active phenotype. Tregs were not associated with fibrosis, but a positive correlation between intrahepatic Tregs and inflammation was found. Taken together, these results suggest a role for Tregs in the pathogenesis of chronic HCV infection.