Myeloid dendritic cells of patients with chronic HCV infection induce proliferation of regulatory T lymphocytes
Department of Medicine, Division of Gastroenterology
Cell Proliferation; Cytokines; 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
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.
DOI of Published Version
Gastroenterology. 2008 Dec;135(6):2119-27. Epub 2008 Aug 7. Link to article on publisher's site
Dolganiuc A, Paek E, Kodys K, Thomas J, Szabo G. (2008). Myeloid dendritic cells of patients with chronic HCV infection induce proliferation of regulatory T lymphocytes. Gastroenterology Publications. https://doi.org/10.1053/j.gastro.2008.07.082. Retrieved from https://escholarship.umassmed.edu/gastroenterology_pp/63