IDO-mediated tryptophan degradation by DCs results in multiple effects, including inhibition of T-cell proliferation, increased T-cell apoptosis, and de novo formation of T_regs. Proinflammatory signals, such as IFN-γ, as well as signals from T cells are known to induce IDO expression in DCs. In particular, CTLA-4 bound to the cell membrane of T_regs activates an IDO-dependent tolerogenic program in DCs. IDO expression by DCs results in inhibition of T-cell effector function, including proliferation and clonal expansion, and reduced survival. Moreover, IDO-expressing DCs may favor the emergence of CD4⁺CD25⁺Foxp3⁺ T_regs by the expansion/conversion from naive CD25⁻Foxp3⁻ T cells.