title: Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis.
abstract: Chronic hepatitis C virus (HCV) infection develops in 85% of exposed individuals and 20% develop cirrhosis. However, the pathogenesis of this process is not well-understood. The objective of this study was to determine whether HCV-reactive T cells play a role in the process of development of cirrhosis during chronic HCV infection. We analyzed 21 human leukocyte antigen (HLA)-A2 patients with chronic HCV infection (9 with histology of inflammation and 12 with histology of fibrosis/cirrhosis). The frequency of CD8(+) T cells reactive to 12 HCV-derived epitopes was determined by an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. The frequency of CD4(+) Th1 and Th2 cells reactive to the HCV core antigen was determined by interferon-gamma and interleukin-5 ELISPOT assays, respectively. Patients with histology of inflammation showed a significantly higher CD8(+) T-cell response to five HCV-derived epitopes (YLLPRRGPRL [core], CINGVCWTV [NS3], LLCPAGHAV [NS3], ILAGYGAGV [NS4B], and GLQDCTMLV [NS5B]) as compared with patients with histology of fibrosis/cirrhosis. Also, patients with histology of inflammation showed a significantly higher CD4(+) Th1 response to the HCV core antigen as compared to patients with histology of fibrosis/cirrhosis. These results indicate that a lack of an optimal T-cell response to HCV is associated with the development of cirrhosis during chronic HCV infection.
authors.affiliation: Department of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Sreenarasimhaiah
authors.forename: Andrés
authors.initials: A
authors.lastname: Jaramillo
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crippin
authors.forename: Mauricio
authors.initials: M
authors.lastname: Lisker-Melman
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005838:Genotype; D015789:HLA-A2 Antigen / Q000032:analysis; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009109:Mumps virus / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015848:Interleukin-5; D010446:Peptide Fragments; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; C448634:influenza matrix peptide (58-66); C069130:nucleocapsid protein, Hepatitis C virus; D007371:Interferon-gamma