Linked Life Data

15494540

Source:http://linkedlifedata.com/resource/pubmed/id/15494540

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-10-20
pubmed:abstractText
CD4 T cells play an important role in hepatitis B virus (HBV) infection by secretion of Th1 cytokines that down-regulate HBV replication, and by promoting CD8 T cell and B cell responses. We have identified and characterized 10 CD4 T cell epitopes within polymerase and used them to analyze the immunological effects of long-term antiviral therapy as compared with spontaneous recovery from HBV infection. Candidate epitopes were tested for binding to 14 HLA-DR molecules and in IFN-gamma ELISPOT and cytotoxicity assays using peripheral blood lymphocytes from 66 HBV-infected patients and 16 uninfected controls. All 10 epitopes bound with high affinity to the most prevalent HLA-DR Ags, were conserved among HBV genomes, and induced IFN-gamma responses from HBV-specific CD4+ T cells. Several epitopes contained nested MHC class I motifs and stimulated HBV-specific IFN-gamma production and cytotoxicity of CD8+ T cells. HBV polymerase-specific responses were more frequent during acute, self-limited hepatitis and after recovery (12 of 18; 67%) than during chronic hepatitis (16 of 48 (33%); p=0.02). Antiviral therapy of chronic patients restored HBV polymerase and core-specific T cell responses during the first year of treatment, but thereafter, responses decreased and, after 3 years, were no more frequent than in untreated patients. Decreased T cell responsiveness during prolonged therapy was associated with increased prevalence of lamivudine-resistant HBV mutants and increased HBV titers. The data provide a rationale for the combination of antiviral and immunostimulatory therapy. These newly described HBV polymerase epitopes could be a valuable component of a therapeutic vaccine for a large and ethnically diverse patient population.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
173
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5863-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15494540-Adult, pubmed-meshheading:15494540-Amino Acid Sequence, pubmed-meshheading:15494540-CD4-Positive T-Lymphocytes, pubmed-meshheading:15494540-Cross Reactions, pubmed-meshheading:15494540-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:15494540-Epitopes, T-Lymphocyte, pubmed-meshheading:15494540-Female, pubmed-meshheading:15494540-Gene Products, pol, pubmed-meshheading:15494540-HLA-DR Antigens, pubmed-meshheading:15494540-Hepatitis B, Chronic, pubmed-meshheading:15494540-Hepatitis B virus, pubmed-meshheading:15494540-Humans, pubmed-meshheading:15494540-Immunity, Cellular, pubmed-meshheading:15494540-Interferon-gamma, pubmed-meshheading:15494540-Male, pubmed-meshheading:15494540-Middle Aged, pubmed-meshheading:15494540-Molecular Sequence Data, pubmed-meshheading:15494540-Peptide Fragments, pubmed-meshheading:15494540-Protein Binding, pubmed-meshheading:15494540-T-Lymphocyte Subsets
pubmed:year
2004
pubmed:articleTitle
Cellular immune responses to the hepatitis B virus polymerase.
pubmed:affiliation
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.