Analysis of T cell repertoire in the liver of patients with chronic hepatitis C.
Many T cells infiltrate into the liver of patients with chronic hepatitis C (CH-C). They are believed to play a crucial role in the immunopathogenesis of hepatic inflammation, but their clonality and specificity are unknown. The aim of this study was to clarify the characteristics of these T cells. We analysed the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) beta-chains by size spectratyping, and determined the sequences of Vbeta CDR3 after subcloning Vbeta-specific polymerase chain reaction products. Spectratyping showed clonal expansions in all liver specimens, most of which showed more than two T cell clones. Moreover, many non-clonal T cells also accumulated in the liver. Clonality of the T cells suspected by spectratyping was confirmed by CDR3 sequencing. Although the sequences revealed no whole CDR3-shared clones among different patients, some common motif sequences were observed. Our data suggest that T cells are stimulated by several hepatitis C virus (HCV) epitopes, then accumulate in the liver of CH-C patients. Shared motifs of expanded T cell clones suggest that they might recognize the same regions of HCV peptides, but have differences due to HCV peptide mutational changes. These clones might also interact with non-clonal T cells and play a crucial role in the immunopathogenesis of CH-C.
Umemura
T
T
Second Department of Internal Medicine, Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Yoshizawa
K
K
Ota
M
M
Katsuyama
Y
Y
Inada
H
H
Tanaka
E
E
Kiyosawa
K
K
D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000145:classification / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta