Inhibition of indoleamine 2,3-dioxygenase activity promotes function of dendritic cells derived from chronic myeloid leukemia

Objective: To investigate the expression of indoleamine 2,3-dioxygenase (IDO) in dendritic cells derived from chronic myeloid leukemia (CML-DCs) and to study the influence of IDO inhibition on the function of CML-DCs. Methods: The expression of IDO mRNA in dendritic cells derived from 17 patients with chronic myeloid leukemia was detected by RT-PCR. The phenotypes of CML-DCs were analyzed by flow cytometry. The immature CML-DCs (imDCs) and the mature CML-DCs (mDCs) were used as stimulating cells and autologous T-lymphocytes were used as reactive cells for a mixed lymphocyte reaction system. IL-12 concentration was detected by ELISA kit; mix lymphocyte reaction was analyzed by MTT assay. Results: It was demonstrated that DCs derived from bone marrow mononuclear cells of CML displayed a typical morphology of DCs. Expressions of co-stimulatory molecules on DCs, such as CD80, CD86, CD83 and HLA-DR, except for CD1a, were obviously higher after maturation (P < 0.05) and were not influenced by 1-Methyltroptophan (1-MT, an inhibitor of IDO). Inhibition IDO activity in mature and immature DCs by 1-MT significantly enhanced their abilities to activate T cells proliferation and to produce IL-12 (P < 0.05, P < 0.01). Conclusion: Inhibition of IDO activity in CML-DCs can increase their abilities to produce IL-12 and activate autologous T cells. Negative regulation of DCs by IDO paves a way for DC-based leukemia immunotherapy.