Induction of Regulatory T-cells and Interleukin-10-producing Cells in Non-responders to Pegylated Interferon-alpha Therapy for Chronic Hepatitis B

Background: Treatment with interferon-alpha (IFN-alpha) leads to a response in only a minority of patients with chronic hepatitis B virus (HBV) infection, but the reasons for this are poorly understood. It was recently shown that in patients with chronic HBV infection, CD4+CD25+ regulatory T-cells (Treg) can suppress the HBV-specific immune response. We aimed to investigate whether in non-responders to IFN-alpha therapy Treg contribute to treatment failure by downregulating the HBV-specific T-cell responses.

Patients And Methods: Fourteen patients positive for hepatitis B e antigen received pegylated IFN-alpha monotherapy for 52 weeks and were followed for 26 weeks.

Results: Compared with non-responders, responders displayed an increased HBV-specific T-helper cell proliferation. At the start of treatment there was no difference in the frequencies of CD4+CD25+ Treg between responders and non-responders. During therapy, the frequency of CD4+CD25+ Treg increased in non-responders, but not in responders. In contrast to the responders, the non-responders showed a significant increase in the frequency of interleukin-10-producing cells. Treg depletion resulted in increased proliferation capacity, but did not affect the frequency of interleukin-10-producing cells measured during the course of the treatment.

Conclusion: This study indicates that Treg might have an important role in HBV persistence during and after pegylated IFN-alpha therapy.