Abstracts (complete list) - Wissenschaft Online

Eva Billerbeck, Hubert E Blum, Robert Thimme
Analysis of virus specific FoxP3+ regulatory CD8+ T cells
Regulatory T cells have been shown to be involved into the suppression of virus specific
T cell responses. Recent studies focused on the regulatory CD4+CD25+ T cell subset,
however, very little information is currently available about the role of regulatory CD8+
T cells in virus infections. To address this important issue, we analyzed the expression
of the regulatory T cell specific transcription factor FoxP3 in HCV-, Flu-, EBV- and CMVspecific
CD8+ T cells from the blood of chronically HCV infected patients and healthy
controls ex vivo and after peptide-specific stimulation. Of note, we did not see a
significant FoxP3 expression in virus-specific CD8+ T cells ex vivo. However, in vitro
stimulation of human PBMC with HCV- or Flu -specific peptides gives rise to two distinct
antigen-specific T cell populations: FoxP3- and FoxP3+ CD8+ T cells. Of note, the
expansion of HCV- and Flu specific FoxP3+ CD8+ T cells was blocked by IL-2- and IL-10neutralizing
antibodies. The HCV- and Flu-specific FoxP3+ CD8+ T cells displayed typical
surface markers of CD4+ regulatory T cells, such as GITR and CTLA-4 and had a cellcell
contact dependent suppressive activity. Interestingly, the stimulation of PBMC with
CMV specific peptides did not induce the generation of virus specific FoxP3+ regulatory
CD8+ T cells. In sum, our results indicate that stimulation with a defined viral antigen
leads to the expansion of two different cell populations: FoxP3- memory/ effector as
well as FoxP3+ regulatory virus-specific CD8+ T cells that may contribute to the
suppression of virus-specific T cells in a strict antigen-specific manner.