T lymphocytes infiltrating the liver during chronic hepatitis C infection express a broad range of T-cell receptor beta chain diversity

Abstract

Background/Aims: During viral chronic hepatitis C (CHC), the intra-hepatic lymphocyte infiltrate is mainly composed of T lymphocytes expressing αβ T-cell receptors (TCR). Since little is known about the TCRαβ diversity of intra-hepatic T lymphocytes (IHL), we evaluated the IHL repertoire from CHC patients ( n=8) as compared to healthy subjects ( n=4), total peripheral blood mononuclear cells, and purified peripheral and intra-hepatic CD8 + cells ( n=2). Methods: The diversity of TCRαβ receptors was evaluated by determining the size and the sequence of the TCRβ chain complementarity determining region 3 (CDR3). The number of total T lymphocytes in liver was estimated by real-time quantitative reverse transcription–polymerase chain reaction of TCRα and CD3ε transcripts. Results: Our results show that transcripts encoding all TCR V beta (BV) families and all TCR J beta (BJ) segments were present in healthy and CHC livers. No biased TCR repertoire, in terms of preferential BV or BJ gene use or restricted CDR3 sequence, was observed in infected livers. When corrected for equivalent numbers of T lymphocytes, BJ segments utilization and CDR3 length diversity were similar in IHL and PBMC, indicating that the TCRβ chain diversity is comparable in both cases. In addition, TCR diversity was similar in both peripheral and intra-hepatic CD8 + T cells. Conclusions: This study shows limited expansions of intra-hepatic T lymphocytes in CHC patients. The increase of T lymphocytes in infected livers correlates with diversification of TCR, arguing for the establishment of a multi-specific immune response.