The immune response initiated by the T-cell response to
viral antigens is thought to be fundamental for viral clearance and disease pathogenesis in hepatitis B virus (HBV)
infection. The T-cell response during acute self-limited
hepatitis B in people is characterised by a vigorous, polyclonal, and multispecific cytotoxic and helper-T-cell response. By contrast, the immune response in chronic carriers, not able to eliminate the virus, is weak or undetectable. Thus a dominant cause of viral persistence could be the existence of a weak
antiviral immune response. Methodological progress in animal models allows more precise investigation of the mechanisms by which the immune system resolves
viral infection or develops
chronic infection. Although clearance of most
virus infections is widely thought to indicate the killing of infected cells by virus-specific T cells, data suggest that non-cytolytic intracellular viral inactivation by
cytokines released by virus-inactivated lymphomononuclear cells could have an important role in the clearance of this virus without killing the infected cell. Additional factors that could contribute to viral persistence, which have been partly proven in animal models, are viral inhibition of antigen processing or presentation, modulation of the response to cytotoxic mediators, immunological tolerance to
viral antigens, viral mutations, and
infection of immunologically privileged sites. In view of the central role of cellular immunity in disease pathogenesis, strategies have been proposed to manipulate this cellular immune response in favour of protection from disease.