DC maturation stages in tolerance induction. The bimodal concept of fully mature DCs as inducers of immunity as opposed to immature DCs as promoters of T-cell tolerance has been recently revisited. It is presently believed that DCs integrate a variety of incoming signals and decide whether protective immunity or Ag-specific unresponsiveness develops.⁷  Current experimental evidence supports the concept that cytokine-modulated semimature DCs promote the conversion of naive T cells into Tr1 cells and/or CD4⁺CD25⁺ Treg cells that inhibit effector T-cell responses via secreted or membrane-bound immunosuppressive cytokines. The inability to produce detectable amounts of bioactive IL-12p70 coupled with enhanced IL-10 release are unique functional features of cytokine-modulated, semimature TDCs.^7,34,39,41  On the contrary, mature DCs might be crucially involved in the expansion of preformed Treg cells, as highlighted by in vitro studies performed with BM-derived, GM-CSF-modulated DCs and by in vivo treatment with complete Freund adjuvant (CFA) and GM-CSF-differentiated DCs.⁹  Illustration by Paulette Dennis.