T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus infections: facts and controversies

In the past few years, we have witnessed extraordinary advances in the understanding of the functions of regulatory T (Treg) cells in immunity against pathogens. However, controversy exists over the part that these cells play in determining the outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, the two main causes of chronic liver inflammation worldwide. Treg-cell responses may be either beneficial or detrimental to those infected with HBV and HCV, by either limiting liver immunopathology or suppressing protective T-cell responses. We review the latest research on CD4 Treg cells, dissect much of the Treg-related HBV and HCV literature, and discuss how new insights in Treg immunobiology apply to human and primate models of HBV and HCV infections. Moreover, we discuss the limitations of the conclusions drawn from current studies on Treg cells, and suggest experimental approaches that can resolve current conflicts and improve our understanding of the roles of Treg-cell subsets in HBV and HCV infections.