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Scand J Immunol. 2003 Apr;57(4):384-90.

Individual and common antigen-recognition sites of liver-derived T cells in patients with autoimmune hepatitis.

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1
Department of Internal Medicine, Johannes-Gutenberg-University Mainz, Langenbeckstrasse 1, 55122 Mainz, Germany. loehr@mail.uni-mainz.de

Abstract

Autoimmune hepatitis (AIH) is characterized by dense T-cell infiltrations in the liver tissue, but little is known how T cells influence the pathogenesis. To address this question, the distribution of T-cell receptor variable beta-chain (TCR Vbeta) transcripts of peripheral blood and liver-infiltrating T cells from previously untreated patients with newly diagnosed acute exacerbated AIH was investigated. Furthermore, the lengths and sequences of complementary-determining region 3 (CDR3) were studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and CDR3 spectratyping revealed multiple clonal expansions of liver-infiltrating T cells but not peripheral T cells within various TCR Vbeta families. Further analysis of overexpressed TCR Vbeta transcripts using TCR beta-chain-joining element (TCR Jbeta)-specific primers in a nested PCR showed characteristic Vbeta/Jbeta combinations. Subsequent sequencing of CDR3 regions from PCR products confirmed the clonality of T-cell expansions and the usage of common and individual CDR3 motifs. In conclusion, the clonality of expanded T cells within the liver tissue during early clinical manifestation of untreated AIH indicated that autoantigen-specific T cells accumulate at the inflammation site. Individual and common CDR3 motifs argued for predominant epitopes that were recognized by liver-infiltrating T cells in AIH patients.

PMID:
12662302
[Indexed for MEDLINE]
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