Unlocking CD8+ T cell potential in chronic hepatitis B virus infection

Advances in 2024 have transformed our understanding of CD8+ T cell dysfunction in chronic hepatitis B virus infection, revealing diverse T cell populations that defy the classic exhaustion model. Studies highlight new therapeutic strategies, such as 4-1BB agonism and TGF beta inhibition, that could rejuvenate these cells and restore antiviral function.Andreata et al.6 identified a self-renewing, long-lived and heterogeneous CD8+ T cell pool displaying a form of dysfunction distinct from classic exhaustion; this pool resists checkpoint inhibition but can be rejuvenated by 4-1BB agonism.Heim et al.7 found a cytotoxic subset of HBV polymerase-specific CD8+ T cells that, though attenuated, retain antiviral potential, regulated by TGF beta signalling.Bosch et al.8 demonstrated how liver sinusoidal endothelial cells modulate HBV-specific CD8+ T cell function, balancing immune activation and tolerance.