Circulating T follicular helper cells are associated with rapid virological response in chronic hepatitis C patients undergoing peginterferon therapy

Abstract

Background: Chronic hepatitis C virus (HCV) infection is associated with abnormal T cell and B cell immune responses. T follicular helper (TFH) cells are a subset of CD4(+) T-helper cells and can activate B cells. This study aimed to investigate the role of circulating CXCR5(+)CD4(+) TFH cells, CD19(+) B cells and the associated cytokines in patients with chronic HCV infection.

Methods: The frequencies and phenotypes of circulating TFH cells and B cell subtypes were characterized using flow cytometry in chronic hepatitis C (CHC) patients and in healthy controls (HCs). The expression of IFN-γ, IL-12p70, IL-5, IL-13, IL-17F, IL-22, IL-23, TGF-β1, IL-10 and IL-21 associated with Th1, Th2, Th17, regulatory T cells (Treg) and TFH cells were analyzed using a Quantibody array. The patients' clinical parameters were detected, and the effect of pegylated interferon plus ribavirin treatment on these immune indicators in CHC patients was determined.

Results: The frequency of CXCR5(+)CD4(+) T cells was significantly higher in CHC patients compared to HCs. There were no significant differences in CD19(+) B cells, CD19(+)CD27(+) B cells, or CD19(+)CD38(+) B cells between CHC patients and HCs. The expressions of cytokines associated with the CD4(+) Th lineage were higher in CHC patients than in HCs, except for IL-21. Patients with rapid virological response (RVR) showed an increased CXCR5(+)CD4(+) T cell count and decreased PD-1(+) CXCR5(+)CD4(+) T cell count compared to non-RVR patients after PEG-IFN/ribavirin treatment.

Conclusions: These data demonstrate that circulating TFH cells and CD4(+) Th lineage-associated cytokines may play a role in HCV-related immune responses.

Keywords: B cells; Cytokines; Hepatitis C virus; Interferon; PD-1; T follicular helper cells.