Figure 1.

Natural killer cells as well as HBV-specific CD8⁺ T cells exhibit their antiviral functions by cytolytic (perforin and granzyme) and/or non-cytolytic (IFN-γ and TNF) mechanisms. However, CD8⁺ T cells express antigen-specific T cell receptors (TCRs) that interact with peptide-MHC I complexes on infected hepatocytes (H) whereas NK cell activation is thought to be antigen-independent. Effector functions and phenotype of both cell types are modulated during acute and chronic HBV infection. Indeed, different mechanisms play a role in regulating both effector populations, such as DCs, immunoregulatory cytokines (IL-10 and/or TGF-β) and expression of several inhibitory receptors. Furthermore, lack of CD4⁺ T cell help and interaction with regulatory T (Treg) cells may lead to CD8⁺ T cell dysfunction in chronically HBV-infected patients resulting in Bim-mediated apoptosis. Importantly, NK cells are also able to inhibit antiviral T cell responses by deleting HBV-specific CD8⁺ T cells in a TRAIL-dependent manner.