T cell immunity in autoimmune hepatitis.
T cells play a central role in the immunopathogenesis of AIH. Until recently CD4+ T cells were thought to be critical for disease development, increasing evidence has shown that CD8+ T and gammadelta T cells also play a significant role. The predisposition of certain HLA genotypes to AIH 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.
Ichiki
Yasunori
Y
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, TB192, One Shields Avenue, Davis, CA 95616, USA.
Aoki
Christopher A
CA
Bowlus
Christopher L
CL
Shimoda
Shinji
S
Ishibashi
Hiromi
H
Gershwin
M Eric
ME
D000818:Animals; D019693:Hepatitis, Autoimmune / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016176:T-Lymphocyte Subsets / Q000276:immunology*