Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells

Abstract

Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide-matured DC and CD4pos T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4pos T cell activation, we observed that a significant fraction of CD4pos T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL-2, IFN-γ, IL-10 and TGF-β. Furthermore, CD4pos T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third-party stimulators were spared. The generation of CD4pos T cells with regulatory function by autologous stimulation did not require the presence of natural CD4posCD25pos regulatory T cells. In addition, the acquisition of regulatory function by CD4posCD25neg T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms. © 2004 Wiley-VCH Verlag GmbH & Co.