目的：观察白细胞介素21（interleukin-21, IL-21）对慢性粒细胞白血病（chronic myeloid leukemia, CML）患者CD4+CD25+调节性T细胞(regulatory T cell, Treg)的作用，为CML的免疫治疗提供新思路。 方法：收集兰州大学第二医院血液科初诊CML患者外周血单个核细胞（peripheral blood mononuclear cells, PBMCs)，免疫磁珠法分选出CD4+T细胞。分别加入50、100、200 ng/ml IL-21与CD4+T细胞共培养72 h后，流式细胞术检测Treg的比例，并设生理盐水空白对照组。Real-time PCR法检测Treg细胞中 Foxp3 mRNA的表达，ELISA法检测各组细胞上清液中IL-10、TGF-β的水平。 结果： 与空白对照组相比，50、100、200 ng/ml IL-21组CD4+CD25+Treg占CD4+T细胞的比例均降低\[（3.42±0.76）%、（6.81±0.33）%、（7.98±076）% vs （12.09±0.91）%，P<0.05\]；且3组的 Foxp3mRNA均降低\[（0.05±0.02）、（0.16±002）、（0.25±0.02） vs 1，P<0.05\]；Treg分泌IL-10量减少\[（26.13±7.28）、(44.88±3.72）、(79.77±3.94） vs (133.00±12.32）pg/ml，P<0.05\]， 分泌TGF-β量也减少\[(9.25±0.84)、(16.70±1.00）、(20.47±1.60）vs (26.05±181）pg/ml，P<0.05\]。 结论： IL-21在体外可减少CML患者外周血中Treg的比例，并抑制其功能。

Objective : To obverse the effect of interleukin-21(IL-21) on CD4+CD25+ regulatory T cells (Tregs) in chronic myeloid leukemia (CML) patients. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from newly diagnosed CML patients in the Hematology Department of Second Hospital of Lanzhou University, and CD4+T cells were isolated by magnetic beads. CD4+T cells were co-cultured with IL-21 (50, 100, and 200 ng/ml) and saline respectively for 72 h, and then the Treg ratio was determined by flow cytometry;  Foxp3 mRNA expression was examined by real-time PCR; and IL-10 and TGF-β in different cell supernatants were detected by ELISA. Results: Compared with the control group, the ratios of Treg in CD4+T cells were decreased in 50 ng/ml, 100 ng/ml and 200 ng/ml IL-21 groups (\[342±0.76\]%, \[6.81±0.33\]%, \[7.98±0.76\]% vs \[12.09±0.91\]%， P<0.05); and  Foxp3 mRNA expressions were also decreased (\[0.05±0.02\], \[0.16±002\], \[0.25±0.02\] vs 1, P<0.05), the levels of IL-10 (\[2613±7.28\], \[44.88±3.72\], \[79.77±394\] vs \[133.00±12.32\] pg/ml, P<0.05) and TGF-β (\[9.25±0.84\], \[16.70±1.00\], \[20.47±1.59\] vs \[26.05±1.81\] pg/ml, P<0.05) in cell supernatants were significantly decreased. Conclusion: IL-21 can inhibit the ratio and function of Treg in peripheral blood of CML patients.

甘肃省科技支撑计划-社会发展计划 (No.0804NKCA115)