T lymphocytes infiltrating the liver during chronic hepatitis C infection express a broad range of T-cell receptor beta chain diversity.
OBJECTIVE
During viral chronic hepatitis C (CHC), the intra-hepatic lymphocyte infiltrate is mainly composed of T lymphocytes expressing alphabeta T-cell receptors (TCR). Since little is known about the TCRalphabeta 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 TCRalphabeta receptors was evaluated by determining the size and the sequence of the TCRbeta 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 TCRalpha and CD3 epsilon 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 TCRbeta 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.
Vigan
Ines
I
Laboratoire d'Immunochimie, CEA-Grenoble, DBMS/ICH, INSERM U548, UJF Grenoble I, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France.
Jouvin-Marche
Evelyne
E
Leroy
Vincent
V
Pernollet
Martine
M
Tongiani-Dashan
Stefania
S
Borel
Eve
E
Delachanal
Elisabeth
E
Colomb
Maurice
M
Zarski
Jean-Pierre
JP
Marche
Patrice N
PN
D000328:Adult; D017252:CD3 Complex; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D014644:Genetic Variation; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D017252:CD3 Complex; C115335:CD3E protein, human; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta