Immune responses to viral pathogens are tightly regulated. During acute viral infections, a strong and multi-specific T cell response is required to control and eliminate the pathogen. Subsequently, the majority of T cells undergo apoptosis, to protect the host from immune mediated damage, and a small subset of cells turn into pathogen-specific memory cells. The processes that mediate T cell expansion, contraction and survival are strongly influenced by various co-stimulatory molecules. Unfortunately, viruses such as Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) have the ability to establish persistence and in such cases, T cells are often functionally impaired or entirely lost. However, the signals that regulate T cell survival and function in chronic viral hepatitis are incompletely understood. We are interested in the characterization of these signals in the context of chronic HBV and HCV infection with a particular focus on the role of co-stimulatory molecules.