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Department of Medicine II, University Hospital Freiburg, Freiburg, Germany
Although FoxP3 has been shown to be the most specific marker for regulatory CD4+ T cells, its significance in the CD8+ T cell population is not well understood. In this study, we show that the in vitro stimulation of human PBMC with hepatitis C virus or Flu virus-specific peptides gives rise to two distinct Ag-specific T cell populations: FoxP3– and FoxP3+CD8+ T cells. The FoxP3+ virus-specific CD8+ T cells share phenotypical markers of regulatory T cells, such as CTLA-4 and glucocorticoid-induced TNFR family-related gene, and do produce moderate amounts of IFN-
but not IL-2 or IL-10. IL-2 and IL-10 are critical cytokines, however, because the expansion of virus-specific FoxP3+CD8+ T cells is blocked by IL-2- or IL-10-neutralizing mAbs. The virus-specific FoxP3+CD8+ T cells have a reduced proliferative capacity, indicating anergy, and display a cell-cell contact-dependent suppressive activity. Taken together, our results indicate that stimulation with a defined viral Ag leads to the expansion of two different cell populations: FoxP3– memory/effector as well as FoxP3+ regulatory virus-specific CD8+ T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant from the Deutsche Forschungsgemeinschaft SFB 620, C6 (to R.T.).
2 Address correspondence and reprint requests to Dr. Robert Thimme, Department of Medicine II, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany. E-mail address: thimme{at}med1.ukl.uni-freiburg.de
3 Abbreviations used in this paper: HCV, hepatitis C virus; GITR, glucocorticoid-induced TNFR family-related gene; Tet, tetramer.
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