Bone marrow-derived dendritic cells reverse the anergic state of CD4+CD25+ T cells without reversing their suppressive function

Dendritic cells (DC) are potent inducers of immunity to foreign Ags, but also contribute to self-tolerance by induction of regulatory T cells or deletion/anergy of self-reactive T cells. In this study, we have studied the capacity of DC to activate naturally occurring CD4(+)CD25(+) regulatory T cells as well as the ability of CD4(+)CD25(+) T cells to suppress the DC-mediated activation of CD4(+)CD25(-) T cells. Mature bone marrow-derived dendritic cells, but not splenic DC, were able to induce the proliferation of CD4(+)CD25(+) T cells in the presence of a polyclonal stimulus and in the absence of exogenous IL-2. The DC-induced proliferative response of the CD4(+)CD25(+) T cells was partially dependent on IL-2 produced by a small number of contaminating CD25(+) effector cells. Because bone marrow-derived dendritic cells induce proliferation of both CD4(+)CD25(+) and CD4(+)CD25(-) T cells in vitro, it was impossible to assay the suppressive function of the CD4(+)CD25(+) T cells using [H-3]TdR uptake or CFSE dilution. We therefore measured IL-2 production in cocultures of CD4(+)CD25(+) and CD4+CD25- T cells using the IL-2 secretion assay. Surprisingly, CD4(+)CD25(+) T cells markedly suppressed IL-2 secretion by the CD4(+)CD25(-) T cells without inhibiting their proliferation. Collectively, these results suggest that Ag presentation by DC can induce the expansion of CD4(+)CD25(+) T cells while simultaneously activating their ability to suppress cytokine secretion by effector T cells.