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作 者:乔淑凯[1] 郭晓楠[1] 任金海[1] 郭晓玲[1] 郭玉洁[1] 蔡圣鑫[1]
机构地区:[1]河北医科大学第二医院血液科,石家庄050000
出 处:《中国免疫学杂志》2016年第1期37-41,共5页Chinese Journal of Immunology
摘 要:目的:观察同种异基因骨密质来源间充质干细胞(CB-MSCs)对小鼠T细胞增殖和分化的影响,探讨其发挥免疫调解作用的分子机制。方法:在体外建立骨密质来源MSCs与异基因小鼠脾淋巴细胞(SP)共培养体系,用MTS/PES法和流式细胞术观察MSCs对SP增殖、凋亡和细胞周期的影响。此外,我们也检测了MSCs共培养对SP中调节性T细胞(Treg)比例以及趋化因子受体CCR5、CCR7和CXCR3表达的影响。结果:异基因骨密质来源MSCs能明显抑制PHA刺激的小鼠SP增殖,其抑制能力呈剂量依赖性;MSCs能够明显抑制共培养体系中SP细胞自发凋亡,并诱导细胞周期G0/G1期阻滞;MSCs与SP共培养后,能明显提高SP中Treg的比例(P<0.01);显著下调T细胞表面CCR5和CXCR3的表达以及明显上调CCR7的表达。结论:异基因CB-MSCs可以明显抑制SP细胞增殖,其机制主要涉及细胞周期G0/G1阻滞而并非诱导凋亡。此外,CBMSCs能通过上调Treg比例和调控趋化因子受体表达等多种途径,来发挥免疫调节作用。Objective:To observe the effects of allogeneic compact bone derived-mesenchymal stem cells (CB-MSCs) on pro- liferation and differentiation of T cells, and investigate the molecular mechanisms of the immunosuppressive ability. Methods : With an established co-culture system of CB-MSCs and mouse spleen lymphocytes (SP) in vitro,we observed the effects of CB-MSCs on prolif- eration, apoptosis and cell cycle of SP by MTS/PES assay and flow cytometry. Also, we measured the effects of CB-MSCs on regulatory T cells (Treg) ratio and expressions of CCR5 ,CCR7 and CXCR3 in SP. Results: CB-MSCs could obviously inhibit the PHA-stimulated SP proliferation with a dose-dependent manner; MSCs could significantly inhibit the spontaneous apoptosis of SP and induce SP cell cycle G0/G1 phase arrest. After co-culture with SP, CB-MSCs could obviously increase the proportion of Treg in SP, down-regulate the expression of CXCR3 and CCRS, as well as up-regulate the expression of CCR7. Conclusion : Allogeneic CB-MSCs can significantly inhibit cell proliferation of SP, the mechanisms mainly involved the GO/G1 cell cycle arrest rather than apoptosis induction. In addition, CB-MSCs can exert immunomodulatory effects by increasing the Treg ratio, regulating the expressions of chemokine receptors.
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