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Journal of Virology, May 2002, p. 5062-5070, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5062-5070.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Abnormal Priming of CD4+ T Cells by Dendritic Cells Expressing Hepatitis C Virus Core and E1 Proteins

Pablo Sarobe,1 Juan José Lasarte,1* Noelia Casares,1 Ascensión López-Díaz de Cerio,1 Elena Baixeras,1 Pablo Labarga,2 Nicolás García,1 Francisco Borrás-Cuesta,1 and Jesús Prieto1

Department of Internal Medicine, Medical School and University Clinic, University of Navarra, 31008 Pamplona,1 Department of Internal Medicine, Hospital San Millán, 26004 Logroño, Spain2

Received 9 November 2001/ Accepted 14 February 2002

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.

* Corresponding author. Mailing address: Department of Internal Medicine, School of Medicine, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain. Phone: 34 948 425600, ext. 6366. Fax: 34 948 425700. E-mail: jjlasarte{at}unav.es.

Journal of Virology, May 2002, p. 5062-5070, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5062-5070.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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