Journal article
Differential dysfunction in dendritic cell subsets during chronic HCV infection
Clinical immunology (Orlando, Fla.), Vol.123(1), pp.40-49
2007
DOI: 10.1016/j.clim.2006.12.001
PMCID: PMC1865520
PMID: 17239662
Abstract
Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease with over 200 million individuals infected worldwide. The vast majority of acutely infected humans develop chronic infection, which is characterized by attenuated antiviral T-cell responses. The mechanisms leading to such attenuation/suppression are poorly understood. It has been proposed that dysfunction of antigen-presenting cells (APC) may underlie the downregulation of antiviral immune responses. However, studies using bulk or
in vitro-derived APC populations have resulted in conflicting reports. In this study, we evaluated the functional and immunophenotypic features of
ex vivo-purified dendritic cell (DC) subsets during chronic HCV infection. We found that plasmacytoid DC (PDC) from HCV-infected patients (HCV-PDC) showed a striking deficit in IFN-α production in response to CpG stimulation. In addition, we found that myeloid DC (MDC) from these patients showed a diminished capacity to induce a mixed lymphocyte response (MLR), correlating with lower levels of HLA-DR and CD86 expression and higher IL-10 production in response to poly-IC stimulation. In contrast, HCV-PDC showed increased ability to stimulate an MLR. Of note, within the HCV-PDC preparation, we noted a distinctly expanded DC subset that expressed some markers of MDC, but showed significantly lower HLA-DR and CD86 expression, suggesting an expansion of DC at an immature/intermediate stage of differentiation. Our studies demonstrate distinct and contrasting dysfunctional features in DC subsets and underscore the importance of evaluating APC subpopulations separately.
Details
- Title: Subtitle
- Differential dysfunction in dendritic cell subsets during chronic HCV infection
- Creators
- Lynn Averill - Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USAWilliam M Lee - Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USANitin J Karandikar - Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Resource Type
- Journal article
- Publication Details
- Clinical immunology (Orlando, Fla.), Vol.123(1), pp.40-49
- DOI
- 10.1016/j.clim.2006.12.001
- PMID
- 17239662
- PMCID
- PMC1865520
- NLM abbreviation
- Clin Immunol
- ISSN
- 1521-6616
- eISSN
- 1521-7035
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2007
- Academic Unit
- Pathology
- Record Identifier
- 9984046907502771
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