Viral Interactions with B-Cells Contribute to Increased Regulatory T-Cells During Chronic HCV Infection
- 1 April 2011
- journal article
- research article
- Published by Mary Ann Liebert Inc in Viral Immunology
- Vol. 24 (2), 119-129
- https://doi.org/10.1089/vim.2010.0077
Abstract
Hepatitis C virus (HCV) has a propensity to establish chronic infection that is characterized by attenuated virus-specific T-cell responses. Mechanisms leading to T-cell attenuation are poorly understood and likely involve dysfunctional interactions between antigen-presenting cells (APC) and effector/regulatory T-cells. Reports on dendritic cells (DC) have described only minor dysfunction during HCV infection. However, there is a paucity of reports regarding B-cell function, despite clear associations with B-cell-related secondary sequelae. In this study we evaluated the state of B-cells during chronic HCV infection, and observed a diminished ability to respond to mitogenic stimuli, correlating with increased apoptosis. This was in contrast to their ex vivo phenotype, which indicated ongoing chronic activation in vivo. There was a high association of HCV-positive strand RNA with B-cells in a subset of HCV patients. Interestingly, ex-vivo-derived HCV RNA-positive B-cells induced significantly greater proliferation in allogeneic T-cells than in HCV-negative B-cells, correlating with an increased generation of CD4+CD25+FOXP3+ regulatory T-cells (Tregs). In-vitro exposure of healthy peripheral blood mononuclear cells (PBMC) to HCV resulted in robust activation of resting B-cells. These HCV-exposed B-cells also showed an enhanced ability to generate Tregs. Our results provide strong evidence for a novel and paradoxical link between HCV-induced enhanced APC function and the generation of Tregs.Keywords
This publication has 51 references indexed in Scilit:
- Identification and In Vitro Expansion of Functional Antigen-Specific CD25 + FoxP3 + Regulatory T Cells in Hepatitis C Virus InfectionJournal of Virology, 2008
- Human regulatory T cells: A unique, stable thymic subset or a reversible peripheral state of differentiation?Immunology Letters, 2007
- Differential dysfunction in dendritic cell subsets during chronic HCV infectionClinical Immunology, 2007
- Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivoJCI Insight, 2006
- Regulatory T Cells Suppress In Vitro Proliferation of Virus-Specific CD8+T Cells during Persistent Hepatitis C Virus InfectionJournal of Virology, 2005
- Production of infectious hepatitis C virus in tissue culture from a cloned viral genomeNature Medicine, 2005
- Isolation and functional analysis of circulating dendritic cells from hepatitis C virus (HCV) RNA-positive and HCV RNA-negative patients with chronic hepatitis C: role of antiviral therapyClinical and Experimental Immunology, 2004
- CD81 (TAPA-1): A MOLECULE INVOLVED IN SIGNAL TRANSDUCTION AND CELL ADHESION IN THE IMMUNE SYSTEMAnnual Review of Immunology, 1998
- Detection of Replicative Form of Hepatitis C Virus RNA in Peripheral Blood Mononuclear CellsThe Journal of Infectious Diseases, 1992
- Infection of peripheral mononuclear blood cells by hepatitis C virusJournal of Hepatology, 1992