DCs in Immune Tolerance in Steady-State Conditions

Abstract

Dendritic cells (DCs) are antigen-presenting cells (APCs) characterized by a unique capacity to stimulate naïve T cells and initiate primary immune responses. Recent studies suggest that DCs are also involved in the induction of immunological tolerance in peripheral tissues under steady-state conditions by maintaining the homeostasis of self-reactive CD4+Foxp3+naturally occurring thymic-derived regulatory T cells (nTregs) and de novo generation of antigen-specific CD4+Foxp3+inducible regulatory T cells (iTregs). We demonstrate here the impact of CD11+DCs on the antigen-specific differentiation of CD4+Foxp3+iTregs from CD4+Foxp3−T cells under steady-state and inflammatory conditions. CD11c+DCs promoted the transforming growth factor (TGF)-β1-mediated conversion of CD4+Foxp3−T cells into CD4+Foxp3+iTregs in vitro, while stimulation of CD11c+DCs with CpG oligodeoxynucleotide (ODN) abrogated this conversion. Furthermore, antigen-specific generation of CD4+Foxp3+iTregs required the function of CD11+DCs under steady-state conditions, whereas such conversion was severely abolished under inflammatory conditions. Thus, these results suggest the crucial role of DCs in the antigen-specific de novo conversion of CD4+Foxp3−T cells into CD4+Foxp3+iTregs under steady-state conditions, thereby leading to the establishment of peripheral immune tolerance.