This Article Full Text Full Text (PDF) Other Versions of this Article: CVI.00141-07v1 14/9/1127    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fan, Z. Articles by Rinaldo, C. R. Search for Related Content PubMed PubMed Citation Articles by Fan, Z. Articles by Rinaldo, C. R., Jr.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, September 2007, p. 1127-1137, Vol. 14, No. 9
1071-412X/07/$08.00+0     doi:10.1128/CVI.00141-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Dendritic Cell Function during Chronic Hepatitis C Virus and Human Immunodeficiency Virus Type 1 Infection

Graduate School of Public Health and School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania,¹ TriCore Reference Laboratories, Albuquerque, New Mexico²

Received 31 March 2007/ Returned for modification 11 June 2007/ Accepted 9 July 2007

Hepatitis C virus (HCV) infection can persist despite HCV-specific T-cell immunity and can have a more aggressive course in persons coinfected with human immunodeficiency virus type 1 (HIV-1). Defects in antigen-presenting, myeloid dendritic cells (DCs) could underlie this T-cell dysfunction. Here we show that monocyte-derived DCs from persons with chronic HCV infection, with or without HIV-1 coinfection, being treated with combination antiretroviral therapy produced lower levels of interleukin 12 (IL-12) p70 in response to CD40 ligand (CD40L), whereas the expression of DC surface activation and costimulatory molecules was unimpaired. The deficiency in IL-12 production could be overcome by addition of gamma interferon (IFN-) with CD40L, resulting in very high, comparable levels of IL-12 production by DCs from HCV- and HIV-1-infected subjects. Smaller amounts of IL-12 p70 were produced by DCs treated with the immune modulators tumor necrosis factor alpha and IL-1β, with or without IFN-, and the amounts did not differ among the uninfected and infected subjects. Blocking of IL-10 with an anti-IL-10 monoclonal antibody in the CD40L-stimulated DC cultures from HCV-infected persons increased the level of IL-12 p70 production. The ability of DCs from HCV-infected persons to stimulate allogeneic CD4⁺ T cells or induce IL-2, IL-5, or IL-10 in a mixed lymphocyte reaction was not impaired. Thus, myeloid DCs derived from persons with chronic HCV infection or with both HCV and HIV-1 infections have defects in IL-12 p70 production related to IL-10 activity that can be overcome by treatment of the DCs with CD40L and IFN-. DCs from these infected subjects have a normal capacity to stimulate CD4⁺ T cells. The functional effectiveness of DCs derived from HCV-infected individuals provides a rationale for the DC-based immunotherapy of chronic HCV infection.

Published ahead of print on 18 July 2007.

This article has been cited by other articles:

• Huang, X.-L., Fan, Z., Borowski, L., Rinaldo, C. R. (2008). Maturation of dendritic cells for enhanced activation of anti-HIV-1 CD8+ T cell immunity. J. Leukoc. Biol. 83: 1530-1540 [Abstract] [Full Text]  
• Saito, K., Ait-Goughoulte, M., Truscott, S. M., Meyer, K., Blazevic, A., Abate, G., Ray, R. B., Hoft, D. F., Ray, R. (2008). Hepatitis C Virus Inhibits Cell Surface Expression of HLA-DR, Prevents Dendritic Cell Maturation, and Induces Interleukin-10 Production. J. Virol. 82: 3320-3328 [Abstract] [Full Text]