Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+ regulatory T cells in hepatitis C virus infection

Ebinuma, Hirotoshi, Nakamoto, Nobuhiro, Li, Yun, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Gostick, Emma, Levine, Bruce L., Tobias, J., Kwok, William W. and Chang, Kyong-Mi 2008. Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+ regulatory T cells in hepatitis C virus infection. Journal of Virology 82 (10) , pp. 5043-5053. 10.1128/JVI.01548-07

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Abstract

CD4+CD25+ regulatory T cells (CD25+ Tregs) play a key role in immune regulation. Since hepatitis C virus (HCV) persists with increased circulating CD4+CD25+ T cells and virus-specific effector T-cell dysfunction, we asked if CD4+CD25+ T cells in HCV-infected individuals are similar to natural Tregs in uninfected individuals and if they include HCV-specific Tregs using the specific Treg marker FoxP3 at the single-cell level. We report that HCV-infected patients display increased circulating FoxP3+ Tregs that are phenotypically and functionally indistinguishable from FoxP3+ Tregs in uninfected subjects. Furthermore, HCV-specific FoxP3+ Tregs were detected in HCV-seropositive persons with antigen-specific expansion, major histocompatibility complex class II/peptide tetramer binding affinity, and preferential suppression of HCV-specific CD8 T cells. Transforming growth factor β contributed to antigen-specific Treg expansion in vitro, suggesting that it may contribute to antigen-specific Treg expansion in vivo. Interestingly, FoxP3 expression was also detected in influenza virus-specific CD4 T cells. In conclusion, functionally active and virus-specific FoxP3+ Tregs are induced in HCV infection, thus providing targeted immune regulation in vivo. Detection of FoxP3 expression in non-HCV-specific CD4 T cells suggests that immune regulation through antigen-specific Treg induction extends beyond HCV.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0022-538X/ (accessed 25/02/2014)
Publisher:	American Society for Microbiology
ISSN:	0022-538X
Date of First Compliant Deposit:	30 March 2016
Last Modified:	20 May 2023 13:40
URI:	https://orca.cardiff.ac.uk/id/eprint/27485

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