T cell repertoire in the liver of patients with autoimmune hepatitis.
Despite a large number of T cells infiltrating into the liver of patients with autoimmune hepatitis (AIH), little is known about their roles or target antigens. To investigate the roles of these T cells in the pathogenesis of AIH, we have studied the clonality of alphabeta T cell populations in liver tissue by size spectratyping the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) Vbeta-chain transcripts. Analysis of nine AIH patients who had the HLA DR4 haplotype showed clonal expansion in all samples. More than two T cell clones expanded in most patients. Although the expression of the TCR Vbeta genes was different among the nine patients, clonal expansion of T cells expressing either TCR Vbeta2, 3, 4, 16, or 22 was observed in two patients or more. TCR Vbeta4 clones expanded in 5 cases. Cloning and sequencing of TCR Vbeta CDR3 from PCR products revealed no whole CDR3-shared clones among different patients. In conclusion, several T cell clonotypes first recognize target antigens, then expand and accumulate in the liver of AIH patients. These suggest heterogeneity of autoantigens and the complexity of AIH immunopathogenesis in individual patients.
Yoshizawa
K
K
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Ota
M
M
Katsuyama
Y
Y
Ichijo
T
T
Inada
H
H
Umemura
T
T
Tanaka
E
E
Kiyosawa
K
K
D000328:Adult; D000595:Amino Acid Sequence; D005260:Female; D019693:Hepatitis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta