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Inhibition of indoleamine 2,3-dioxygenase activity promotes function of dendritic cells derived from chronic myeloid leukemia
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Abstract:
Objective:To investigate the expression of indoleamine 2,3dioxygenase (IDO) in dendritic cells derived from chronic myeloid leukemia（CMLDCs）and to study the influence of IDO inhibition on the function of CMLDCs. Methods: The expression of IDO mRNA in dendritic cells derived from 17 patients with chronic myeloid leukemia was detected by RTPCR. The phenotypes of CMLDCs were analyzed by flow cytometry. The immature CMLDCs (imDCs) and the mature CMLDCs (mDCs) were used as stimulating cells and autologous Tlymphocytes were used as reactive cells for a mixed lymphocyte reaction system. IL12 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 costimulatory molecules on DCs, such as CD80, CD86, CD83 and HLADR, except for CD1a, were obviously higher after maturation (P<0.05) and were not influenced by 1Methyltroptophan(1MT, an inhibitor of IDO). Inhibition IDO activity in mature and immature DCs by 1MT significantly enhanced their abilities to activate T cells proliferation and to produce IL12 (P<0.05,P<0.01).Conclusion: Inhibition of IDO activity in CMLDCs can increase their abilities to produce IL12 and activate autologous T cells. Negative regulation of DCs by IDO paves a way for DCbased leukemia immunotherapy.
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Project Supported:
Supported by the Major State Basic Research Development Program of China (973 Program) (No.2004CB518804); Supported by the National Natural Science Funds for Distinguished Young Scholars (No.30325043)
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