【摘要】 目的探讨髓系来源抑制细胞(myeloid-derived suppressor cells,MDSCs)在急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)不同疾病状态下的数量分布情况,并探讨其在介导ALL肿瘤免疫逃逸过程中的免疫抑制作用。方法通过流式细胞术测定初发未治、治疗后缓解和复发难治ALL患者外周血单个核细胞中MDSCs细胞的比例,并采用定量PCR法检测Foxp3 mRNA的表达水平,以健康人外周血为对照组。分离不同疾病状态ALL患者的MDSCs细胞与健康人T淋巴细胞共培养,观察其抑制T淋巴细胞增殖的情况。结果复发难治组外周血中的MDSCs数量所占比例高于初发未治组、缓解组以及对照组,而初发未治组又高于缓解组以及对照组(均P<0.05)。Foxp3 mRNA水平在复发难治组中最高,其次为初发未治组。患者外周血中MDSCs与健康人T淋巴细胞共培养第5天和第7天时,初发未治组和复发难治组T细胞增殖水平均低于缓解组(均P<0.05)。结论初发和复发ALL患者中存在MDSCs数量扩增,且Foxp3 mRNA表达水平增高。MDSCs可能通过抑制正常T淋巴细胞增殖或诱导调节性T细胞产生介导肿瘤免疫逃逸,从而导致ALL的发生和复发。更多还原

【Abstract】 Objective To investigate the proportion of myeloid derived suppressor cells( MDSCs) and its immunosuppressive effects in acute lymphoblastic leukemia( ALL) of different clinical stages. Methods The proportion of MDSCs in the peripheral blood mononuclear cells( PBMCs) was examined by flow cytometry in ALL patients at the stages of onset,remission and relapse. Quantitative RT-PCR was used to detect the expression level of Foxp3 mRNA. Peripheral blood samples from healthy persons were used as controls. The MDSCs isolated from PBMCs of ALL patients of different stages were co-cultured with normal T lymphocytes,and the inhibitory effect of MDSCs on the proliferation of T lymphocytes was analyzed. Results The number of MDSCs in PBMCs from ALL patients of relapse stage was significantly higher than that from patients of onset stage,remission stage or healthy controls. Among the latter three groups,ALL patients of onset stage showed the highest number of MDSCs( P < 0. 05). Besides,the expression level of Foxp3 mRNA was highest in relapsed ALL patients,followed by onset patients. MDSCs from onset and relapsed patients significantly inhibited the proliferation of normal T lymphocytes when co-cultured for 5 and 7 days. Conclusion In newly diagnosed and relapsed ALL patients,the number of MDSCs is increased and expression of Foxp3 mRNA is upregulated,which may inhibit T lymphocyte proliferation and lead to the occurrence and recurrence of ALL.更多还原