title: Determinants of in vitro expansion of different human virus-specific FoxP3+ regulatory CD8+ T cells in chronic hepatitis C virus infection.
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 virus-specific CD8+ T cells differs among distinct virus-specific CD8+ T-cell populations depending on the differentiation status.
authors.affiliation: Spemann Graduate School of Biology and Medicine, University of Freiburg, Germany.|Faculty of Biology, University of Freiburg, Germany.|Department of Medicine II, University Hospital Freiburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Billerbeck
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakamoto
authors.affiliation: Department of Medicine II, University Hospital Freiburg, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Seigel
authors.affiliation: Department of Medicine II, University Hospital Freiburg, Germany.
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kyong-Mi
authors.initials: KM
authors.lastname: Chang
authors.affiliation: Department of Medicine II, University Hospital Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme