Limited T cell receptor Vbeta-chain repertoire of liver-infiltrating T cells in autoimmune hepatitis

Abstract

Background/aims: To characterize the cellular immune reactions in autoimmune hepatitis, the T cell receptor repertoire of liver-infiltrating and circulating T cells was studied.

Methods: Nucleic acids of liver-tissue and peripheral blood-derived T cells from 12 patients with untreated autoimmune hepatitis, four patients with chronic hepatitis C and three patients with toxic liver injury were extracted and analysed using a semiquantitative RT-PCR with a panel of T cell receptor Vbeta family specific primers. After agarose gel electrophoresis, the distribution of T cell receptor (TCR) Vbeta molecules was assessed by densitometry. Furthermore, results were compared to the TCR Vbeta distribution of 10 healthy blood donors.

Results: Four of 12 patients with untreated autoimmune hepatitis but no patients with chronic hepatitis C and toxic liver injury showed a significant overexpression of TCR Vbeta3 (17.8% +/- 2.6% vs. 9.3% +/- 4.6%; p = 0.01) and three an overexpression of Vbeta13.1 (14.6% +/- 2.3% vs. 6.6% +/- 3.5%; p = 0.02) molecules compared to the TCR Vbeta-distribution in healthy blood donors. In addition, Vbeta3+ T cells were found enriched in the liver tissue compared to autologous peripheral blood in three autoimmune hepatitis patients (15.3% +/- 7.0% vs. 5.2% +/- 3.1%; L/B ratio: 2.9), while Vbeta13.1+ T cells were enriched in the liver tissue from one of three patients with overexpression.

Conclusions: In autoimmune hepatitis a disease specific compartmentalisation of TCR Vbeta3+ T cells was observed in the liver tissues. Although their specificity was unknown, this might indicate that these infiltrating T cells could have relevance for abnormal immunoregulation.