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Updated: Aug 8, 2026
Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
Intrahepatic CD8+ T-lymphocyte response is important for therapy-induced viral clearance in chronic hepatitis B
Thjon J Tang1, Jaap Kwekkeboom, Shanta Mancham
1Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Room L-455, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Background/Aims:
To determine which immune cells contribute to HBV-clearance during antiviral therapy, we performed a longitudinal analysis of intrahepatic immune cells during interferon-alpha therapy of chronic HBV-patients using the FNAB technique.
Methods:
Twenty chronic HBeAg+-patients were treated with pegylated alpha-interferon combined with lamivudine or placebo for 52 weeks. FNAB and blood specimens were obtained at week 0, 2, 8 and 52. CD4+- and CD8+ T-lymphocytes, CD56+ cells, IFNgamma and granzyme B (GrB) were immunocytochemically quantified.
Results:
The relative numbers of CD56+ cells and CD8+ T-lymphocytes were significantly higher in FNAB compared to blood at all time-points. Responders (n=9) exhibited significant increases in intrahepatic CD8+ and CD8+GrB+ lymphocytes, a small elevation in CD8+IFNgamma+ T-lymphocytes, no change in CD4+ T-lymphocytes, and a decrease in intrahepatic CD56+ cells during the first weeks of therapy. In non-responders (n=11) no significant changes in CD4+- and CD8+ T-lymphocytes and an increase in intrahepatic and CD56+ cells were observed during therapy.
Conclusions:
The intrahepatic CD8+ T-lymphocyte, but not the CD4+ T-lymphocyte or NK/NKT-cell response, is important for HBV clearance during interferon-alpha therapy, and the antiviral effect may be mediated by both cytolytic and non-cytolytic mechanisms.
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