Evolution of the Intrahepatic T Cell Repertoire during Chronic Hepatitis C Virus Infection

Abstract

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.

T cell receptor variable β gene repertoire in liver and peripheral blood lymphocytes of chronically hepatitis C virus-infected patients with and without mixed cryoglobulinaemia

“…The size and diversity of HCV‐specific T cell populations in the liver and their relevance for the outcome of HCV infection are still poorly known . Currently, whether unsuccessful immune response is targeted against fewer antigens or consists of smaller effector T cell populations is one of the major questions being investigated.…”

Narrowing of T‐cell receptor beta variable repertoire during symptomatic herpesvirus infection in transplant patients

“…In autoimmune diseases (for example, multiple sclerosis), clonal expansions occur in the myelin basic protein‐specific T‐cell population, 20 , 21 , 22 with the cells expressing a common amino‐acid motif in the CDR3 region of unrelated individuals 23 . In addition, studies of liver‐infiltrating hepatitis C‐specific T cells in patients with chronic HCV infection have revealed a diverse TCR repertoire 24 , 25 . Finally, there are already published cases that show that CD8 + TCR diversity is linked with immune protection and lacks viral escape mutations 26 , 27 .…”

“…23 In addition, studies of liver-infiltrating hepatitis C-specific T cells in patients with chronic HCV infection have revealed a diverse TCR repertoire. 24,25 Finally, there are already published cases that show that CD8 + TCR diversity is linked with immune protection and lacks viral escape mutations. 26,27 All these studies suggest that the maintenance of repertoire diversity is essential in controlling virus spread and preventing disease development.…”