title: Abnormal priming of CD4(+) T cells by dendritic cells expressing hepatitis C virus core and E1 proteins.
abstract: Patients infected with hepatitis C virus (HCV) have an impaired response against HCV antigens while keeping immune competence for other antigens. We hypothesized that expression of HCV proteins in infected dendritic cells (DC) might impair their antigen-presenting function, leading to a defective anti-HCV T-cell immunity. To test this hypothesis, DC from normal donors were transduced with an adenovirus coding for HCV core and E1 proteins and these cells (DC-CE1) were used to stimulate T lymphocytes. DC-CE1 were poor stimulators of allogeneic reactions and of autologous primary and secondary proliferative responses. Autologous T cells stimulated with DC-CE1 exhibited a pattern of incomplete activation characterized by enhanced CD25 expression but reduced interleukin 2 production. The same pattern of incomplete lymphocyte activation was observed in CD4(+) T cells responding to HCV core in patients with chronic HCV infection. However, CD4(+) response to HCV core was normal in patients who cleared HCV after alpha interferon therapy. Moreover, a normal CD4(+) response to tetanus toxoid was found in both chronic HCV carriers and patients who had eliminated the infection. Our results suggest that expression of HCV structural antigens in infected DC disturbs their antigen-presenting function, leading to incomplete activation of anti-HCV-specific T cells and chronicity of infection. However, presentation of unrelated antigens by noninfected DC would allow normal T-cell immunity to other pathogens.
authors.affiliation: Department of Internal Medicine, Medical School and University Clinic, University of Navarra, 31008 Pamplona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Sarobe
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: Noelia
authors.initials: N
authors.lastname: Casares
authors.forename: Ascensión
authors.initials: A
authors.lastname: López-Díaz de Cerio
authors.forename: Elena
authors.initials: E
authors.lastname: Baixeras
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Nicolás
authors.initials: N
authors.lastname: García
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrás-Cuesta
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005260:Female; D005822:Genetic Vectors; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D014161:Transduction, Genetic; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: C087035:E1 protein, Hepatitis C virus; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; C069130:nucleocapsid protein, Hepatitis C virus