T cell immunity in autoimmune hepatitis

T cells play a central role in the immunopathogenesis of AM. Until recently CD4(+) T cells were thought to be critical for disease development, increasing evidence has shown that CD8(+) T and gamma delta T cells also play a significant role. The predisposition of certain HLA genotypes to AM as well as the clonal expansion of a limited number of T cell receptors suggests that the presentation of a self-antigen or a molecular mimic may be responsible for the initiation of the immune response. Given the association of AIH with viral hepatitis, it is thought that the loss of tolerance begins with an infection of hepatocytes and subsequent cytolysis by CD8(+) T cells. The presentation of self-antigens or molecular mimics leads to activation and clonal expansion of T cells; this process may be increased by impaired regulatory T cells and a defect in apoptosis. Ultimately T cells initiate B cell production of autoantibodies, proinflammatory cytokines and finally hepatocyte cytotoxicity. (c) 2005 Elsevier B.V. All rights reserved.