The characteristics and functions of CD4+CD25+ regulatory cells have been well defined in murine and human systems. However, the interaction between CD4+CD25+ T cells and dendritic cells (DC) remains unclear. In this study, we examined the effect of human CD4+CD25+ T cells on maturation and function of monocyte-derived DC. We show that regulatory T cells render the DC inefficient as APCs despite prestimulation with CD40 ligand. This effect was marginally reverted by neutralizing Abs to TGF-β. There was an increased IL-10 secretion and reduced expression of costimulatory molecules in DC. Thus, in addition to direct suppressor effect on CD4+ T cells, regulatory T cells may modulate the immune response through DC.