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

Hirotoshi Ebinuma, Nobuhiro Nakamoto, Yun Li, David A. Price, Emma Gostick, Bruce L. Levine, J. Tobias, William W. Kwok, Kyong Mi Chang

Research output: Contribution to journalArticle

127 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5043-5053
Number of pages11
JournalJournal of Virology
Volume82
Issue number10
DOIs
Publication statusPublished - 2008 May
Externally publishedYes

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Interleukin-2 Receptor alpha Subunit
Hepatitis C virus
Virus Diseases
Regulatory T-Lymphocytes
Hepacivirus
T-lymphocytes
antigens
infection
T-Lymphocytes
Antigens
Viruses
viruses
In Vitro Techniques
transforming growth factors
major histocompatibility complex
Transforming Growth Factors
Orthomyxoviridae
Major Histocompatibility Complex
peptides

ASJC Scopus subject areas

  • Immunology

Cite this

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 A.; Gostick, Emma; Levine, Bruce L.; Tobias, J.; Kwok, William W.; Chang, Kyong Mi.

In: Journal of Virology, Vol. 82, No. 10, 05.2008, p. 5043-5053.

Research output: Contribution to journalArticle

Ebinuma, Hirotoshi ; Nakamoto, Nobuhiro ; Li, Yun ; Price, David A. ; Gostick, Emma ; Levine, Bruce L. ; Tobias, J. ; Kwok, William W. ; Chang, Kyong Mi. / Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+ regulatory T cells in hepatitis C virus infection. In: Journal of Virology. 2008 ; Vol. 82, No. 10. pp. 5043-5053.
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