Matured human monocyte-derived dendritic cells (MoDCs) induce expansion of CD4+CD25+FOXP3+ T cells lacking regulatory properties.

Naturally occurring CD4(+)CD25(+) T regulatory cells (nTregs) play a key role as suppressors in immune mechanisms that protect against self-destruction. The forkhead box p3 transcription factor (FOXP3) has a central role in the development of nTregs. We show here that co-culture of naïve T cells with flagellin-exposed monocyte-derived dendritic cells (MoDCs) generates CD4(+)CD25(+)FOXP3(+) T cells that transiently express FOXP3 together with CD25 but do not suppress proliferation of CD4(+)CD25(-) T cells. Moreover, purified CD4(+)CD25(+)FOXP3(+) T cells reveal a different proliferation and cytokine production profile from that of nTregs. These data indicate that in the presence of ongoing immune responses a T cell antigenic phenotype superimposable of that of nTregs does not necessarily predict suppressive function and that FOXP3 in humans is not sufficient for development and function of regulatory T cells.