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Lamivudine treatment can overcome cytotoxic T‐cell hyporesponsiveness in chronic hepatitis B: New perspectives for immune therapy
Author(s) -
Boni Carolina,
Penna Amalia,
Ogg Graham S.,
Bertoletti Antonio,
Pilli Massimo,
Cavallo Cristina,
Cavalli Albertina,
Urbani Simona,
Boehme Richard,
Panebianco Ruggero,
Fiaccadori Franco,
Ferrari Carlo
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.23045
Subject(s) - ctl* , lamivudine , cytotoxic t cell , immunology , medicine , hepatitis b virus , immune system , hepatitis b , viral load , t cell , virology , cd8 , virus , biology , in vitro , biochemistry
The hepatitis B virus (HBV) cytotoxic T lymphocyte (CTL) response in patients with chronic HBV infection is generally weak or totally undetectable. This inability to mount protective CTL responses is believed to be a crucial determinant of viral persistence, and its correction represents an important objective of immune therapies for chronic hepatitis B. However, amplification of CTL responses in vivo may be ineffective if HBV‐specific CD8 cells are either absent or nonresponsive to exogenous stimulation. In this study, we asked whether antiviral treatments able to inhibit viral replication and to reduce viral and antigen load can successfully reconstitute CTL responses creating the appropriate conditions for their therapeutic stimulation. For this purpose, the HBV‐specific CTL response before and during lamivudine therapy was studied longitudinally in 6 HLA‐A2–positive patients with HBeAg+ chronic hepatitis B. Both HBV‐specific cytotoxic T cell activity measured by chromium release assay on peptide stimulation in vitro and CD8+ T cell frequency measured ex vivo by HLA‐A2/peptide tetramer staining were significantly augmented by lamivudine therapy. This enhancement followed the reconstitution of CD4 reactivity and the decline of viral load induced by therapy. Our study shows that lamivudine treatment in chronic hepatitis B can restore CTL reactivity, making CTL susceptible to exogenous stimulation. This effect may enhance the probability that T cell‐based immune therapies delivered after lamivudine treatment can successfully reconstitute a protective CTL response able to cure chronic HBV infection. (H EPATOLOGY 2001;33:963‐971.)