标题: Immune and Viral Profile from Tolerance to Hepatitis B Surface Antigen Clearance [打印本页] 作者: StephenW 时间: 2011-2-14 20:14 标题: Immune and Viral Profile from Tolerance to Hepatitis B Surface Antigen Clearance
Immune and Viral Profile from Tolerance to Hepatitis B Surface Antigen
Clearance: a Longitudinal Study of Vertically Hepatitis B Virus-Infected
Children on Combined Therapy
Ivana Carey,1 Lorenzo D'Antiga,1 Sanjay Bansal,1 Maria Serena Longhi,1 Yun Ma,1
Irene Rebollo Mesa,2 Giorgina Mieli-Vergani,1 and Diego Vergani1*
Institute of Liver Studies and Paediatric Liver Centre, King's College London
School of Medicine at King's College Hospital, Denmark Hill, London SE5 9RS,
United Kingdom,1 MRC Centre for Transplantation, King's College London School of
Medicine at Guy's Hospital, St. Thomas Street, London, SE1 9RT, United Kingdom2
Received 12 July 2010/ Accepted 2 December 2010
The aim of the study was to investigate longitudinally hepatitis B virus
(HBV)-specific T-cell reactivity and viral behavior versus treatment response in
tolerant children during combined antiviral therapy. Twenty-three children with
infancy-acquired hepatitis B (HBeAg+) belonging to a published pilot study of
1-year treatment with lamivudine/alpha interferon (IFN-) were investigated. Five
seroconverted to anti-HBs (responders). Nine were HLA-A2+ (4 responders and 5
nonresponders). Mutations within the HBV core gene were determined at baseline
in liver and in serial serum samples by direct sequencing at baseline; during
treatment week 2 (TW2), TW9, TW28, and TW52; and after follow-up week 24 (FUW24)
and FUW52. HBV-specific reactivity was evaluated by T-cell proliferation with 16
HBV core 20-mer overlapping peptides and by HLA-A2-restricted core18-27 pentamer
staining and CD8+ IFN- enzyme-linked immunospot (ELISPOT) assay. HBV
core-specific T-cell proliferative and CD8 responses were more vigorous and
broader among responders than among nonresponders at TW28 and TW52, while the
number of mutations within HBV core gene immunodominant epitopes was lower at
TW28 and was negatively associated with HBV-specific T-cell proliferative
responses at both time points. The HBV DNA viral load was negatively associated
with HBV-specific T-cell proliferative and CD8 responses during treatment,
especially at TW28. Treatment-induced transition from immunotolerance to HBV
immune control is characterized by the emergence of efficient virus-specific
immune responses capable of restraining mutations and preventing viral evasion.
菀凯里,一德Antiga洛伦佐,1邦萨尔桑杰,1玛丽亚小威隆吉,1恽码,1
艾琳Rebollo梅萨,2 Giorgina Mieli - Vergani,1和迭戈Vergani1 *