T cell immunity in autoimmune hepatitis
, Christopher A. Aoki
, Christopher L. Bowlus
, Shinji Shimoda
, M. Eric Gershwin
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, TB192,
One Shields Avenue, Davis, CA 95616, USA
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku,
Fukuoka 812-8582, Japan
Clinical Research Center, Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan
Division of Gastroenterology, Department of Internal Medicine, University of California Davis, Davis, CA 95616, USA
Received 13 November 2004; accepted 11 January 2005
Available online 15 February 2005
1568-9972/$ - see front matter D 2005 Elsevier B.V. All rights reserved.
Abbreviations: PBC, primary biliary cirrhosis; AIH, autoimmune hepatitis; ALT, alanine aminotransferase; AMA, anti-mitochondrial
antibodies; ASGP-R, asialoglycoprotein receptor; AST, aspartate aminotransferase; HBV, hepatitis B virus; CDR, complementarily-determining
region; CTL, cytotoxic T lymphocyte; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; IFN-g, interferon-g; IP-10, IFN-inducible
protein; LFA, lymphocyte function-associated antigen; LKM-1, liver kidney microsomal type 1; PBC, primary biliary cirrhosis; PBMC,
peripheral blood mononuclear cells; PSC, primary sclerosing cholangitis; TCR, T cell receptor; TGF-h, transforming growth factor-h; TNF-a,
tumor necrosis factor-a.
T Corresponding author. Tel.: +1 530 752 2884; fax: +1 530 752 4669.
E-mail address: firstname.lastname@example.org (M.E. Gershwin).
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 gy 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
D 2005 Elsevier B.V. All rights reserved.
Keywords: Autoimmune hepatitis; T cell receptor; Autoreactive T cells; Molecular mimicry; Autoantibodies
Autoimmunity Reviews 4 (2005) 315 – 321