Indoleamine 2,3-dioxygenase production by human dendritic cells results inthe inhibition of T cell proliferation

Dendritic cells (DCs) play a key role in the activation and regulation of B and T lymphocytes, Production of indoleamine 2,3-dioxygenase (IDO) by macr ophages has recently been described to result in inhibition of T cell proli feration through tryptophan degradation. Since DCs can be derived from mono cytes, we sought to determine whether DCs could produce IDO which could pot entially regulate T cell proliferation. Northern blot analysis of RNA from cultured monocyte-derived human DC revealed that IDO mRNA was induced upon activation with CD40 ligand and IFN-gamma. IDO produced from activated DCs was functionally active and capable of metabolizing tryptophan to kynurenin e. Activated T cells were also capable of inducing IDO production by DCs, w hich was inhibited by a neutralizing Ab against IFN-gamma, DC production of IDO resulted in inhibition of T cell proliferation, which could be prevent ed using the IDO inhibitor 1-methyl-DL-tryptophan. These results suggest th at activation of DCs induces the production of functional IDO, which causes depletion of tryptophan and subsequent inhibition of T cell proliferation. This may represent a potential mechanism for DCs to regulate the immune re sponse.