title: T lymphocytes infiltrating the liver during chronic hepatitis C infection express a broad range of T-cell receptor beta chain diversity.
abstract: 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.
authors.affiliation: Laboratoire d'Immunochimie, CEA-Grenoble, DBMS/ICH, INSERM U548, UJF Grenoble I, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France.
authors.forename: Ines
authors.initials: I
authors.lastname: Vigan
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jouvin-Marche
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.forename: Martine
authors.initials: M
authors.lastname: Pernollet
authors.forename: Stefania
authors.initials: S
authors.lastname: Tongiani-Dashan
authors.forename: Eve
authors.initials: E
authors.lastname: Borel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Delachanal
authors.forename: Maurice
authors.initials: M
authors.lastname: Colomb
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Marche
mesh_terms: 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*
chemical_list: D017252:CD3 Complex; C115335:CD3E protein, human; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta