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

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Bibliographische Detailangaben
Zeitschriftentitel: Journal of General Virology
Personen und Körperschaften: Billerbeck, Eva, Nakamoto, Nobuhiro, Seigel, Bianca, Blum, Hubert E., Chang, Kyong-Mi, Thimme, Robert
In: Journal of General Virology, 90, 2009, 7, S. 1692-1701
Format: E-Article
Sprache: Englisch
veröffentlicht:
Microbiology Society
Schlagwörter:
Virology
Details
Zusammenfassung: <jats:p>It has been shown previously that suppressive virus-specific FoxP3<jats:sup>+</jats:sup> regulatory CD8<jats:sup>+</jats:sup> T cells can be expanded from human peripheral blood mononuclear cells after <jats:italic>in vitro</jats:italic> antigen-specific stimulation. This study extended this finding by analysing the mechanisms of virus-specific FoxP3<jats:sup>+</jats:sup> regulatory CD8<jats:sup>+</jats:sup> T-cell generation during peptide-specific expansion <jats:italic>in vitro</jats:italic>. It was shown that hepatitis C virus (HCV)-, influenza virus (FLU)-, Epstein–Barr virus (EBV)- and cytomegalovirus (HCMV)-specific FoxP3<jats:sup>+</jats:sup> regulatory CD8<jats:sup>+</jats:sup> T cells could be expanded differentially from the blood of chronically HCV-infected patients following <jats:italic>in vitro</jats:italic> peptide-specific stimulation. The different ability of virus-specific CD8<jats:sup>+</jats:sup> T-cell populations to express FoxP3 after continuous antigen stimulation <jats:italic>in vitro</jats:italic> correlated significantly with the <jats:italic>ex vivo</jats:italic> differentiation status. Indeed, CD27<jats:sup>+</jats:sup> CD28<jats:sup>+</jats:sup> CD57<jats:sup>−</jats:sup> HCV-, FLU- and EBV-specific CD8<jats:sup>+</jats:sup> T cells displayed a significantly higher ability to give rise to FoxP3<jats:sup>+</jats:sup> regulatory CD8<jats:sup>+</jats:sup> T cells compared with CD27<jats:sup>−</jats:sup> CD28<jats:sup>−</jats:sup> CD57<jats:sup>+</jats:sup> HCMV-specific CD8<jats:sup>+</jats:sup> T cells. Similar T-cell receptor expression patterns of FoxP3<jats:sup>+</jats:sup> versus FoxP3<jats:sup>−</jats:sup> CD8<jats:sup>+</jats:sup> T cells of the same antigen specificity indicated that both cell populations were probably expanded from the same virus-specific CD8<jats:sup>+</jats:sup> T-cell precursor. In addition, no specific antigen-presenting cell populations were required for the generation of FoxP3<jats:sup>+</jats:sup> CD8<jats:sup>+</jats:sup> T cells, as CD8<jats:sup>+</jats:sup>-selected virus-specific FoxP3<jats:sup>+</jats:sup> CD8<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> regulatory CD8<jats:sup>+</jats:sup> T cells from virus-specific CD8<jats:sup>+</jats:sup> T cells differs among distinct virus-specific CD8<jats:sup>+</jats:sup> T-cell populations depending on the differentiation status.</jats:p>
Umfang: 1692-1701
ISSN: 1465-2099
0022-1317
DOI: 10.1099/vir.0.009837-0