髓源性抑制细胞在肾移植受者不同免疫状态的动态变化

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目的:检测肾移植受者不同免疫状态外周血中髓源性抑制细胞(MDSC)的水平,探讨肾移植受者外周血中MDSC的变化规律及MDSC在免疫状态评估中的作用。方法:收集2016年10月至2017年5月于郑州大学第一附属医院肾移植科行肾移植手术的30例受者术前及术后1、7、14、30、90 d的外周血单个核细胞,采用流式细胞术检测MDSC的细胞比例;以健康正常人作为对照,流式细胞术检测肾移植术后肾功能稳定组、肺部感染组和急性排斥组外周血MDSC比例,采用两独立样本n t检验和单因素方差分析统计学方法进行分析。n 结果:以移植术前1 d水平[(2.02±1.90)%、(0.39±0.30)%、(1.63±1.48)%]作为基线,肾移植受者外周血MDSC、单核样髓源性抑制细胞(Mo-MDSC)、粒细胞样髓源性抑制细胞(G-MDSC)水平均于术后1 d大幅度上升[(6.76±4.85)%,(1.21±0.85)%,(5.55±3.01)%]且显著高于术前水平(n P0.05);肾移植受者Mo-MDSC于术后1 d显著低于对照供者[(1.21±0.85)%比 (2.19±1.08)%,n t=2.95,n P<0.05],术后14 d显著高于对照供者[(0.56±0.48)%比 (0.31±0.21)%,n t=1.586,n P<0.05];G-MDSC术后14 d显著高于对照供者[(1.99±1.01)%比 (1.04±0.46)%,n t=2.885,n P<0.05],其他时间点两组间比较差异无统计学意义;相较于正常人[(1.79±1.48)%、(0.34±0.29)%]、尿毒症患者[(1.92±1.58)%、(0.39±0.29)%]及移植肾功能稳定组受者[(2.36±2.30)%、(0.62±0.42)%],肾移植术后感染组患者外周血中MDSC与Mo-MDSC[(3.80±3.47)%、(1.90±1.72)%]比例显著升高,差异有统计学意义(n P0.05);急性排斥反应组患者外周血MDSC与G-MDSC[(1.28±1.18)%、(0.89±0.75)%]明显降低,与术后肾功能稳定组受者比较差异有统计学意义(n t=2.543、3.785,n P<0.05),与正常人、尿毒症患者间差异无统计学意义,Mo-MDSC[(0.47±0.53)%]在各组之间的差异比较无统计学意义。n 结论:肾移植受者体内MDSC扩增早期受手术炎性反应影响,后期和免疫抑制及免疫稳态形成密切相关;Mo-MDSC主要发挥抑制受者炎性反应,而G-MDSC的动员与排斥反应的免疫抑制作用更为相关。“,”Objective:To explore the changes of myeloid-derived suppressor cells (MDSCs) in renal transplant recipients under different immune states and to analyze the correlation between those cells, so as to assess their roles under different immune states in renal transplantation.Methods:The peripheral blood was collected in 30 recipients undergoing renal transplantation in our hospital from October 2016 to May 2017, at the 1st day before surgery and 1st, 7th, 14th, 30th and 90th day after surgery. Flow cytometry was used to detect the dynamic changes of MDSCs. Flow cytometry was used to compare the levels of MDSCs in peripheral blood of stable graft function group, pathogen infection group and acute rejection group after renal transplantation. Two independent samples n t test and one-way analysis of variance statistical methods were used for analysis.n Results:Taking the level at 1st before transplantation [(2.02±1.90)%, (0.39±0.30)%, (1.63±1.48)%] as the baseline, the proportion of MDSCs, monocyte MDSCs (Mo-MDSC), and granulocyte-MDSCs (G-MDSCs) in peripheral blood increased significantly [(6.76±4.85)%, (1.21±0.85)%, (5.55±3.01)%] at 1st day after transplantation (alln P0.05); The proportion of Mo-MDSCs at 1st day after transplantation in kidney transplant recipients was lower than that in the control donor [(1.21±0.85)% vs. (2.19±1.08)%,n t=2.95, n P<0.05], and that on the postoperative day 14 was significantly higher than in the control donor [(0.56±0.48)% vs. (0.31±0.21)%,n t=1.586, n P<0.05]; The proportion of G-MDSCs on the postoperative day 14 was significantly higher than that in control donors [(1.99±1.01)% vs. (1.04±0.46)%,n t=2.885, n P<0.05], and at other time points there was no statistically significant difference between the two groups; As compared with normal people [(1.79±1.48)%, (0.34±0.29)%], uremia patients [(1.92±1.58)%, (0.39±0.29)%] and recipients with the stable renal transplant function [(2.36±2.30)%, (0.62±0.42)%], the proportion of MDSCs and Mo-MDSCs [(3.80±3.47)%, (1.90±1.72)%] in peripheral blood of patients with infection after renal transplantation increased significantly (n P0.05). The proportion of MDSCs and G-MDSCs in peripheral blood of patients with acute rejection [(1.28±1.18)%, (0.89±0.75)%] was significantly reduced as compared with that of recipients with the stable renal function after transplantation (n t=2.543, 3.785, n P<0.05), and there was no significant difference between normal people or uremia patients and the patients with acute rejection. There was no statistically significant difference in the proportion of Mo-MDSCs [(0.47±0.53)%] among the groups.n Conclusion:Early amplification and activation of MDSCs protect the body against inflammation. In the steady state of graft function, MDSCs may assist in the formation of immune balance. Mo-MDSCs mainly play an inhibitory role in the inflammatory response of infected recipients. G-MDSCs mobilization is likely to protect against acute rejection.
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