Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans

Expression of the transcription factor Foxp3 (forkhead box P3) has been implicated as a key element for CD25+ T regulatory cell function in mice. However, literature over similar involvement of FOXP3 expression in human T regulatory cells is limited. We found that, unlike murine cells, FOXP3 mRNA expression could be induced in human CD25− and CD8+ peripheral blood mononuclear cells, which were both negative for FOXP3 mRNA expression after isolation. Expression of FOXP3 mRNA began as soon as 24-40 hours after stimulation, demonstrating a correlation between activation and FOXP3 mRNA expression in human cells. In order to determine whether FOXP3 expression is confined to CD4+CD25+ T cells with a regulatory phenotype, we analyzed several well-defined T-cell clones and lines with various specificities. Surprisingly, expression of FOXP3 mRNA was detected in all clones and limited to the CD25hi populations. Nonetheless, the CD25hi fraction did not display regulatory properties because both the CD25hi and CD25low populations exhibited a similar proliferative- and interferon-γ-secreting potential after antigenic stimulation. These results indicate that FOXP3 expression in humans, unlike mice, may not be specific for cells with a regulatory phenotype and may be only a consequence of activation status.