Induction of anergic and regulatory T cells by plasmacytoid dendritic cells and other dendritic cell subsets

The induction of antigen-specific tolerance is critical for maintaining immune homeostasis and preventing autoimmunity. Because the central tolerance that eliminates potentially harmful autoreactive T cells is incomplete, peripheral mechanisms for suppressing self-reactive T cells play an important role. Dendritic cells (DCs) are professional antigen-presenting cells, which have an extraordinary capacity to stimulate naive T cells and initiate primary immune responses. Recent accumulating evidence indicates that several subsets of human DCs also play a critical role in the induction of peripheral tolerance by anergizing effector CD4(+) and CD8(+) T cells or by inducing the differentiation of naive T cells into T-regulatory cells, which produce interleukin (IL)-10. Human DC subsets with the property of suppressing an antigen-specific T-cell response include plasmacytoid DCs, which are either in an immature state or in a mature state induced by CD40 ligand stimulation, and monocyte-derived DCs, which are either in an immature state or have had their state modulated by treatment with IL-10 or CD8(+)CD28(-) T cells. These "tolerogenic" DCs may be relevant to therapeutic applications for autoimmune and allergic diseases as well as organ transplant rejection.