In Vitro Analysis of Hepatitis B Virus Specific CD4+ T Cells

Chronic infection with the hepatitis B virus (HBV) is estimated to affect 350 million persons worldwide and continues to be an important cause of morbidity and mortality (1 ). It is generally accepted that the host immune response plays a key role in the course and outcome of HBV infection. In chronic HBV infection the immune responses are weak, narrowly focused, and impaired. In contrast, effective and long-term control over viral replication is associated with vigorous HBV-specific T-cell responses (2 ). Studies of patients with spontaneous resolution of HBV infection have shown that the activation of hepatitis B nucleocapsid (HBcAg) specific CD4⁺ T lymphocytes is a prerequisite for control over viral replication and hepatitis B surface antigen (HBsAg) clearance (3 ,4 ). This HBcAg protein is the strongest immunogen for HLA class II restricted T-cell responses, and therefore most assays analyzing the CD4 immune responses in HBV have focused on this antigen (2 ,5 ).