Viral interactions with B-cells contribute to increased regulatory T-cells during chronic HCV infection

Chris L Ayers; Mihail Firan; Vinodh Pillai; William M Lee; Nitin J Karandikar

doi:10.1089/vim.2010.0077

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Viral interactions with B-cells contribute to increased regulatory T-cells during chronic HCV infection

Journal article

Open access

Peer reviewed

Viral interactions with B-cells contribute to increased regulatory T-cells during chronic HCV infection

Chris L Ayers, Mihail Firan, Vinodh Pillai, William M Lee and Nitin J Karandikar

Viral immunology, Vol.24(2), pp.119-129

04/2011

DOI: 10.1089/vim.2010.0077

PMCID: PMC3070003

PMID: 21449722

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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.

Cell Proliferation

Hepacivirus - immunology

Lymphocyte Activation

Humans

Middle Aged

Male

T-Lymphocytes, Regulatory - immunology

B-Lymphocytes - immunology

CD4 Antigens - analysis

Forkhead Transcription Factors - analysis

Hepatitis C, Chronic - immunology

Interleukin-2 Receptor alpha Subunit - analysis

Adult

Female

T-Lymphocytes, Regulatory - chemistry

Apoptosis

Details

Title: Subtitle: Viral interactions with B-cells contribute to increased regulatory T-cells during chronic HCV infection
Creators: Chris L Ayers - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9072, USA
Mihail Firan
Vinodh Pillai
William M Lee
Nitin J Karandikar
Resource Type: Journal article
Publication Details: Viral immunology, Vol.24(2), pp.119-129
DOI: 10.1089/vim.2010.0077
PMID: 21449722
PMCID: PMC3070003
NLM abbreviation: Viral Immunol
ISSN: 0882-8245
eISSN: 1557-8976
Publisher: United States
Language: English
Date published: 04/2011
Academic Unit: Pathology
Record Identifier: 9984047727602771

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