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

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 beta 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.

• Authors: Hirotoshi Ebinuma, Nobuhiro Nakamoto, Yun Li, David A Price, Emma Gostick, Bruce L Levine, J Tobias, William W Kwok, Kyong-Mi Chang
• Journal: Journal of virology (J Virol) Vol. 82 Issue 10 Pg. 5043-53 (May 2008) ISSN: 1098-5514 [Electronic] United States
• PMID: 18337568 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CD4 Antigens
• FOXP3 protein, human
• Forkhead Transcription Factors
• Histocompatibility Antigens Class II
• Interleukin-2 Receptor alpha Subunit
• Transforming Growth Factor beta

Topics

• CD4 Antigens (analysis)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Proliferation
• Cells, Cultured
• Flow Cytometry
• Forkhead Transcription Factors (analysis)
• Hepacivirus (immunology)
• Hepatitis C (immunology)
• Histocompatibility Antigens Class II (metabolism)
• Humans
• Interleukin-2 Receptor alpha Subunit (analysis)
• Protein Binding
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Regulatory (chemistry, immunology)
• Transforming Growth Factor beta (metabolism)