Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection is characterized by a weak immune response to HBV. Regulatory T cells (T reg ) can suppress the function of effector T cells and may thus be key players in this impaired immune response. Changes in the functionality or number of T reg could explain the decreased antiviral response in chronic HBV patients. To investigate the role of T reg in chronic HBV infection, we compared the proportional frequency and functionality of T reg in peripheral blood of 50 chronic HBV patients, 23 healthy controls, and 9 individuals with a resolved HBV infection. A higher percentage of T reg , defined as CD4, CD25, CD45RO, and cytotoxic T‐lymphocyte–associated antigen 4–positive cells, was detected within the population of CD4 + cells in peripheral blood of chronic HBV patients compared with healthy controls and individuals with a resolved HBV infection. Accordingly, chronic HBV patients displayed a higher FoxP3 messenger RNA level than healthy controls. Depletion of CD25 + cells from peripheral blood mononuclear cells (PBMC) of chronic HBV patients resulted in an enhanced proliferation after stimulation with HBV core antigen. Reconstitution of these depleted PBMC with CD4 + CD25 + T reg resulted in a dose‐dependent reduction of both HBV‐specific proliferation and interferon γ production. In conclusion , chronic HBV patients harbor an increased percentage of T reg in peripheral blood compared with controls. T reg have an immunosuppressive effect on HBV‐specific T helper cells. The presence of HBV‐specific T reg could contribute to an inadequate immune response against the virus, leading to chronic infection. (H EPATOLOGY 2005;41:771–778.)