Recent studies indicate that several mechanisms may be involved in the loss of the function of HBV-specific T cells during chronic hepatitis B. It was shown that high-level viremia negatively influences the virus-specific immune responses. High viral replication in the liver with viral load higher than 10 7 copies/mL is correlating with hyporesponsiveness of virus-specific CD8 + T cells in patients with chronic hepatitis B [23] . Moreover, the prolonged exposure to viral antigens occurring during the chronic viral infections can trigger the T cells to become tolerant and prone to apoptosis. The interaction between programmed death 1 (PD-1) receptor and its ligand PD-L1 (also known as B7-H1) plays an important role to prevent an overreaction of the immune system [24] . Recent studies revealed that inhibitory molecules such as PD-1 and CTLA-4 are markedly upregulated on virus-specific T cells, resulting in exhaustion (e.g., lack of IFNγ production and proliferation) [25] . Simultaneously, this mechanism can contribute to the development of the chronic infection by impairment of the effective antiviral response. This hypothesis was previously proven for hepatitis C virus (HCV) [26, 27] and human immunodeficiency virus (HIV) infection in humans [28] [29] [30] , as well as lymphocytic choriomeningitis virus (LCMV) infection in mice [31, 32] , and more recently for HBV [33, 34] . Furthermore, several studies imply that functional defects of antigen presenting cells (APCs), mainly dendritic cells (DCs), may contribute to the impaired T cell response in chronic hepatitis B patients [35] [36] [37] [38] [39] [40] [41] . In vitro studies showed that DCs isolated from HBV chronic carriers produce lower amount of antiviral cytokines, such as type I interferons and TNFα, in comparison to healthy controls [35, 36] . In addition, those DCs are less efficient in T cell activation and stimulation of T cell proliferation [35, [39] [40] [41] . The novel report demonstrated that myeloid DCs from chronic HBV patients express increased level of inhibitory PD-L1 molecule and therefore may down regulate functions of HBV-specific T cells [39] . Several investigations underline the significance of CD4 + CD25 + regulatory T cells in pathogenesis of persistent viral infections [42] . In HCVand HIV-infected patients, it was shown that regulatory T cells may downregulate HCV-and HIV-specific CD8 + and therefore influence the disease progression [43] [44] [45] . The role of regulatory T cells in HBV infection is still not clear. Nevertheless, the increased numbers of CD4 + CD25 + regulatory T cells were detected in the blood and the liver of patients with chronic severe hepatitis B [46] . In addition, the liver itself is an organ with tolerogenic properties that might contribute to the immunological tolerance during chronic HBV infection [47, 48] . Finally, viruses developed the strategies to efficiently evade the host immune response resulting in persistent infections. Viral immune escape due to the mutation of CD4 + , CD8 + , and B cell epitopes in a given HLA background have been observed in patients infected with HIV, HCV, and HBV [49] [50] [51] [52] [53] [54] .