Myeloid dendritic cells of patients with chronic HCV infection induce proliferation of regulatory T lymphocytes
UMass Chan Affiliations
Department of Medicine, Division of GastroenterologyDocument Type
Journal ArticlePublication Date
2008-10-07Keywords
Cell ProliferationCytokines
Dendritic Cells
Disease Progression
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Gene Expression
Hepatitis C, Chronic
Humans
Myeloid Cells
RNA
T-Lymphocytes, Regulatory
Gastroenterology
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
BACKGROUND and AIMS: Dendritic cells (DCs) initiate and sustain an efficient T-lymphocyte response. Chronic hepatitis C virus (HCV) infection is associated with inefficient T-cell functions that fail to eradicate the virus, so defects in DC function might be involved in HCV pathogenesis. This study analyzed the activities of myeloid DCs and distinct CD4(+) T-cell populations in samples collected from patients with HCV. METHODS: The abilities of primary BDCA1(+) or monocyte-derived DCs from HCV patients (HCV-DC) to stimulate CD4(+), CD4(+)CD25(-), or different ratios of CD4(+)CD25(+)/CD4(+)CD25(-) T cells were evaluated in mixed lymphocyte reactions. T-cell proliferation and phenotype were evaluated by flow cytometry; cytokine production was evaluated by enzyme-linked immunosorbent assay and marker expression by polymerase chain reaction analyses. RESULTS: HCV-DCs were poor activators of CD4(+) T cells; this defect was reversed by addition of interleukin-2, neutralization of interleukin-10, or elimination of CD4(+)CD25(+) T cells. HCV-DC stimulated proliferation of regulatory T cells (Tregs; CD4(+)CD25(+)FoxP3(+)), which limit proliferation of HCV-specific T lymphocytes. We observed an increased frequency of CD4(+)CD25(+) T cells in peripheral blood of HCV patients and that HCV-DC overexpressed a number of alternative costimulatory molecules, including PD-L1. Finally, HCV-DC stimulated expansion rather than de novo induction of FoxP3(+) Tregs. CONCLUSIONS: Our results indicate a role for myeloid DC in expansion of Tregs to promote chronic infection of patients with HCV.Source
Gastroenterology. 2008 Dec;135(6):2119-27. Epub 2008 Aug 7. Link to article on publisher's siteDOI
10.1053/j.gastro.2008.07.082Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31139PubMed ID
18835391Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1053/j.gastro.2008.07.082