目的: 研究吲哚胺2，3双加氧酶（indoleamine 2，3dioxygenase，IDO）在慢性粒细胞性白血病源性树突状细胞（dendritic cells derived from chronic myeloid leukemia，CMLDCs）中的表达，及抑制IDO活性对CMLDCs免疫刺激功能的影响。方法: RTPCR检测17例患者CMLDCs的IDO mRNA的表达情况，流式细胞仪检测CMLDCs免疫表型。在有或无IDO抑制剂1甲基色氨酸（1methyltroptophan,1MT）作用下，分别以不成熟CMLDCs（imDCs）和成熟CMLDCs（mDCs）为刺激细胞，完全缓解期（complete remission，CR）CML患者外周T淋巴细胞为反应细胞建立混合淋巴细胞反应体系，ELISA法检测CMLDCs上清液IL12水平，MTT法检测CMLDCs刺激自体T淋巴细胞的增殖能力。结果: 随着CMLDCs的诱导分化和成熟，IDO mRNA表达逐渐上调；经TNFα诱导的DCs免疫表型除CD1a外，CD80、CD86、CD83、HLADR的表达均明显上调(P<005)，且上述分子的表达不受1MT的影响。用1MT抑制IDO活性后的imDCs和mDCs，其IL12水平均明显增加(P<005，P<001)，且激发自体T淋巴细胞增殖的能力也明显增强(P<0.05，P<0.01)。结论: 抑制IDO活性可提高CMLDCs的IL12分泌水平，增强其对自体T细胞增殖的刺激能力，IDO对DCs的负性调节为白血病生物治疗提供了新的思路。

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.

国家重点基础研究计划（973）资助项目 (No.2004 CB 518804);国家自然科学基金杰出青年项目 (No.30325043)