Determinants of in vitro expansion of different human virus-specific FoxP3+ regulatory CD8+ T cells in chronic hepatitis C virus infection

Eva K. Billerbeck, Nobuhiro Nakamoto, Bianca Seigel, Hubert E. Blum, Kyong Mi Chang, Robert Thimme

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

It has been shown previously that suppressive virus-specific FoxP3+ regulatory CD8+ T cells can be expanded from human peripheral blood mononuclear cells after in vitro antigen-specific stimulation. This study extended this finding by analysing the mechanisms of virus-specific FoxP3+ regulatory CD8+ T-cell generation during peptide-specific expansion in vitro. It was shown that hepatitis C virus (HCV)-, influenza virus (FLU)-, Epstein-Barr virus (EBV)- and cytomegalovirus (HCMV)-specific FoxP3+ regulatory CD8+ T cells could be expanded differentially from the blood of chronically HCV-infected patients following in vitro peptide-specific stimulation. The different ability of virus-specific CD8+ T-cell populations to express FoxP3 after continuous antigen stimulation in vitro correlated significantly with the ex vivo differentiation status. Indeed, CD27+ CD28+ CD57- HCV-, FLU- and EBV-specific CD8+ T cells displayed a significantly higher ability to give rise to FoxP3+ regulatory CD8+ T cells compared with CD27- CD28- CD57+ HCMV-specific CD8+ T cells. Similar T-cell receptor expression patterns of FoxP3+ versus FoxP3- CD8+ T cells of the same antigen specificity indicated that both cell populations were probably expanded from the same virus-specific CD8+ T-cell precursor. In addition, no specific antigen-presenting cell populations were required for the generation of FoxP3+ CD8+ T cells, as CD8+-selected virus-specific FoxP3+ CD8+ T cells could be expanded by peptide presentation in the absence of antigen-presenting cells. Taken together, these results suggest that the ability to expand FoxP3+ regulatory CD8+ T cells from virusspecific CD8+ T cells differs among distinct virus-specific CD8+ T-cell populations depending on the differentiation status.

Original languageEnglish (US)
Pages (from-to)1692-1701
Number of pages10
JournalJournal of General Virology
Volume90
Issue number7
DOIs
StatePublished - Oct 5 2009
Externally publishedYes

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Chronic Hepatitis C
Virus Diseases
Regulatory T-Lymphocytes
Hepacivirus
Viruses
T-Lymphocytes
Antigen-Presenting Cells
Human Herpesvirus 4
Antigens
Peptides
Population
T-Lymphoid Precursor Cells
In Vitro Techniques
T-Cell Antigen Receptor
Orthomyxoviridae
Cytomegalovirus
Blood Cells

ASJC Scopus subject areas

  • Virology

Cite this

Determinants of in vitro expansion of different human virus-specific FoxP3+ regulatory CD8+ T cells in chronic hepatitis C virus infection. / Billerbeck, Eva K.; Nakamoto, Nobuhiro; Seigel, Bianca; Blum, Hubert E.; Chang, Kyong Mi; Thimme, Robert.

In: Journal of General Virology, Vol. 90, No. 7, 05.10.2009, p. 1692-1701.

Research output: Contribution to journalArticle

Billerbeck, Eva K. ; Nakamoto, Nobuhiro ; Seigel, Bianca ; Blum, Hubert E. ; Chang, Kyong Mi ; Thimme, Robert. / Determinants of in vitro expansion of different human virus-specific FoxP3+ regulatory CD8+ T cells in chronic hepatitis C virus infection. In: Journal of General Virology. 2009 ; Vol. 90, No. 7. pp. 1692-1701.
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