TY - JOUR
T1 - Parallel expansion of human virus-specific FoxP3- effector memory and de novo-generated FoxP3+ regulatory CD8+ T cells upon antigen recognition in vitro
AU - Billerbeck, Eva
AU - Blum, Hubert E.
AU - Thimme, Robert
PY - 2007/7/15
Y1 - 2007/7/15
N2 - 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-γ 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.
AB - 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-γ 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.
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U2 - 10.4049/jimmunol.179.2.1039
DO - 10.4049/jimmunol.179.2.1039
M3 - Article
C2 - 17617596
AN - SCOPUS:34548730876
SN - 0022-1767
VL - 179
SP - 1039
EP - 1048
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -