Regulatory T Cells in Chronic Hepatitis B Virus Infection

textabstractWorldwide 400 million people suffer from chronic hepatitis B virus (HBV) infection and approximately 1 million people die annually from HBV-related disease. To clear HBV, an effective immune response, in which several cell types and cytokines play a role, is important. It is known that patients who develop a chronic infection lack the vigorous multi-specifi c T cell response with a type 1 cytokine profi le necessary to clear the virus. One cell type that could play a role in the absence of an adequate T cell response are CD4+CD25+ regulatory T cells (Treg). These Treg are capable of inhibiting the adaptive T cell response. In chapter 2 of this thesis the proportion of Treg in the peripheral blood of patients with a chronic HBV infection, individuals with a resolved HBV infection and healthy controls was compared. Patients with a chronic HBV infection showed an increased proportion of peripheral blood Treg compared to the two other groups. Depletion of Treg resulted in an enhanced in vitro response to HBV core antigen (HBcAg). Reconstitution of Treg-depleted cells with isolated Treg showed that Treg inhibited the proliferation and interferon (IFN)-γ production to HBcAg in a dose dependent manner. Therefore, Treg appear to be a mediator of the impaired antiviral response observed in patients with a chronic HBV infection