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This Article Full Text Full Text (PDF) All Versions of this Article: vir.0.009837-0v1 90/7/1692    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Billerbeck, E. Articles by Thimme, R. PubMed PubMed Citation Articles by Billerbeck, E. Articles by Thimme, R. Agricola Articles by Billerbeck, E. Articles by Thimme, R.

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

¹ Department of Medicine II, University Hospital Freiburg, Germany
² Faculty of Biology, University of Freiburg, Germany
³ Spemann Graduate School of Biology and Medicine, University of Freiburg, Germany
⁴ University of Pennsylvania, Philadelphia, PA, USA

Correspondence
Robert Thimme
robert.thimme{at}uniklinik-freiburg.de

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.