Parallel expansion of human virus-specific FoxP3- effector memory and de novo-generated FoxP3+ regulatory CD8+ T cells upon antigen recognition in vitro

被引:57
作者
Billerbeck, Eva [1 ]
Blum, Hubert E. [1 ]
Thimme, Robert [1 ]
机构
[1] Univ Hosp, Dept Med 2, D-79106 Freiburg, Germany
关键词
D O I
10.4049/jimmunol.179.2.1039
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-gamma 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.
引用
收藏
页码:1039 / 1048
页数:10
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