Parallel expansion of human virus-specific FoxP3- effector memory and de novo-generated FoxP3+ regulatory CD8+ T cells upon antigen recognition in vitro.
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.
Billerbeck
Eva
E
Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.
Blum
Hubert E
HE
Thimme
Robert
R
D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015789:HLA-A2 Antigen; D007376:Interleukin-2