Pegylated interferon α enhances recovery of memory T cells in e antigen positive chronic hepatitis B patients

Background: Interferons (IFNs) are a group of cytokines commonly used in the clinical treatment of chronic hepatitis B (CHB) patients. Their therapeutic effects are highly correlated with recovery of host antiviral immunity. Clearance of hepatitis B virus (HBV) is mediated partially by activated functional memory T cells. The aims of the present study were to investigate memory T cell status in patients with different outcomes following pegylated interferon-alpha (IFN-alpha) therapy and to identify new biomarkers for predicting antiviral immune responses. Methods: Peripheral blood cells were isolated from 23 CHB patients who were treated with pegylated IFN-alpha at week 0 (baseline) and week 24. Co-expression of programmed death-1 (PD-1) and CD244 in CD45RO positive T cells, as well as a subset of CD127 and CXCR4 positive memory T cells were assessed. In addition, perforin, granzyme B, and interferon-gamma (IFN-gamma) expressions were also analyzed by flow cytometric analysis after intracytoplasmic cytokine staining (ICCS). Peripheral blood mononuclear cells (PBMC) isolated at week 24 were re-challenged with exogenous HBV core antigen, and the percentage of IFN-gamma expression, serum HBV DNA loads, and ALT (alanine aminotransferase) levels were evaluated. Results: At week 24, PD-1 and CD244 expression in CD8 memory T cells were down-regulated (P < 0.05, P < 0.05, respectively), along with decreased HBV DNA loads (P < 0.05), while the expressions of partial effector molecules in CD8 and CD4 memory T cells was up-regulated (P < 0.05, P < 0.05, respectively), especially in the responders. CD127 and CXCR4 were highly expressed in CD8 memory T cells after pegylated IFN-alpha treatment (P < 0.05), which was inversely correlated with HBV DNA loads (r = -0.47, P = 0.001). The responders had a higher IFN-gamma expression in memory T cells than the non-responders did after HBV antigen re-stimulation in vitro. Conclusion: Pegylated IFN-alpha treatment enhanced recovery of memory T cells in CHB patients by down-regulating inhibitory receptors and up-regulating effector molecules. The expressions of CXCR4 and CD127 in CD8 memory T cell may be used as biomarkers for predicting the outcome of treatment.