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DCs in Immune Tolerance in Steady-State Conditions

互联网

614
Dendritic cells (DCs) are antigen-presenting cells (APCs) characterized by a unique capacity to stimulate na�ve 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.
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