Evolution of the intrahepatic T cell repertoire during chronic hepatitis C virus infection.
Chronic hepatitis C virus (HCV) infection is characterized by extensive infiltration of inflammatory cells in the liver, where there is a compartmentalization of HCV-reactive T lymphocytes. Previous studies have demonstrated a broad intrahepatic TCR repertoire; however, there is little information regarding the stability of this intrahepatic T cell population. We studied the T cell repertoires in sequential liver biopsy samples from five individuals with chronic HCV infection using TCR spectratype analysis; four subjects had been treated with IFN-alpha during the interval between biopsies. Transcripts from most TCRBV families were detectable in the liver tissues, and 25-85% of these had skewed spectratype profiles indicative of T cell clonal expansions. Most of the intrahepatic T cell expansions were not evident in an analysis of peripheral blood T cells collected at the same time as the liver biopsy. Detailed analysis using TCRBJ-primed run-off reactions revealed that the intrahepatic TCR repertoires were not stable within an individual, although some TCR clonotypes were maintained for at least 45 months.
Giuggio
Vicki M
VM
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA 01655, USA.
Bonkovsky
Herbert L
HL
Rothman
Alan L
AL
D001706:Biopsy; D022801:Complementarity Determining Regions / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D008099:Liver / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*
D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D007371:Interferon-gamma