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.