Regulatory Phenotype, PD-1 and TLR3 Expression in T Cells and Monocytes from HCV Patients Undergoing Antiviral Therapy: A Randomized Clinical Trial

BACKGROUND & AIMS: The cellular immunity has a profound impact on the status of hepatitis C virus (HCV) infection. However, the response of cellular immunity on the virological response in patients with antiviral treatment remains largely unclear. We aimed to clarify the response of peripheral T cells and monocytes in chronic hepatitis C patients with antiviral treatment. METHODS: Patients with chronic hepatitis C were treated either with interferon alpha-2b plus ribavirin (n = 37) or with pegylated interferon alpha-2a plus ribavirin (n = 33) for up to 24 weeks. Frequencies of peripheral regulatory T-cells (Tregs), programmed death-1 (PD-1) expressing CD4(+) T-cells or CD8(+) T-cells and toll-like receptor (TLR) 3 expressing CD14(+) monocytes were evaluated by flow cytometry in patients at baseline, 12 and 24 weeks following treatment and in 20 healthy controls. RESULTS: Frequencies of Tregs, PD-1 and TLR3 expressing cells were higher in patients than those in control subjects (P<0.05). Patients with complete early virological response (cEVR) showed lower Tregs, PD-1 expressing CD4(+) or CD8(+) T-cells than those without cEVR at 12 weeks (P<0.05). Patients with low TLR3 expressing CD14(+) monocytes at baseline had a high rate of cEVR (P<0.05). CONCLUSIONS: Low peripheral TLR3 expressing CD14(+) monocytes at baseline could serve as a predictor for cEVR of antiviral therapy in chronic HCV-infected patients. The cEVR rates were significantly increased in the patients with reduced circulating Tregs, PD-1 expressing CD4(+) or CD8(+) T-cells. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR10001090.