Exploring Replicative Senescence Of Hepatitis B Virus-specific Cytotoxic T Lymphocytes In Patients With Chronic Hepatitis B

More than 400 million people worldwide are persistently infected with the hepatitis B virus (HBV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. The ability to clear HBV after infection has been associated with the presence of a strong HBV-specific cytotoxic T lymphocytes (CTLs) response. However, the main immunological feature that characterizes chronically infected patients is a state of relative hyporesponsiveness of HBV-specific CTLs compared with that demonstrable in acute self-limited hepatitis B patients.HBV-specific CTLs of chronic hepatitis B (CHB) patients couldn't expand when stimulated with antigen peptides in vitro, while HBV-specific CTLs of acute self-limited hepatitis B patients and resolved patients could expand vigorously. The difference in peptide induced CTLs proliferation has not been explained till now. Clone expanding is the fundamental function of T lymphocytes. During persistent infections, the principal determining viral control has been suggested to be the ability of virus-specific CTLs to clonally expand, and the antiviral effector functions are always coupled with clonally expand. So elucidating the reason why HBV-specific CTLs of CHB patients couldn't expand may be the key to explain the hyporesponsiveness of HBV-specific CTLs.Studies have suggested that chronic stimulation can result in the development of specific CTLs that are incapable of cell division. Such a failure to proliferate is generally attributed to replicative senescence. The key feature of senescent T cells is the loss of CD28, the dominant costimulatory receptor required for the induction and maintenance of T-cell-mediated immunity. Senescent T cells also possess other features: these cells express a variety of natural killer-associated receptors (NKRs) and are resistant to apoptosis, most...