Figure 1.

Differentiation of monocyte-derived tolerogenic DCs. DCs differentiate from DC precursors in the peripheral blood under the influence of IL-4 and GM-CSF in vitro into immature DCs (iDCs). Repetitive stimulations of T cells with iDCs result in the induction of anergic/regulatory T cells (Tregs). In the presence of sufficient maturation signals, which are provided by bacterial components via toll-like receptors or by distinct combinations of proinflammatory cytokines, DCs mature into a migratory/stimulatory phenotype. Incubation of iDCs with several mediators or genetic modification of DCs in the presence or absence of maturation factors can lead to the generation of tolerogenic DCs, which inhibit effector/cytotoxic T cells responses by induction of anergy, apoptosis, or Tregs.