摘要
目的:研究胎盘蛋白14(PP14)增强调节性T细胞(Treg细胞)诱导滤泡调节性T细胞(Tfr细胞)增殖的作用及机制。方法:分离健康志愿者外周血中的淋巴细胞;磁珠分选淋巴细胞中的Treg细胞;流式检测CD4^+CD25^+Foxp3Treg细胞比例及其表面CTLA-4和HLA-G的表达;ELISA检测上清中IL-10和TGF-β的浓度;采用Transwell小室进行Treg细胞和淋巴细胞的共培养实验;流式检测淋巴细胞中CD4^+CXCR5^+Foxp3^+Tfr细胞的比例。结果:相对于对照组,PP14组Treg细胞的比例增加了1.26倍(t=4.748,P=0.009 0),而其表面CTLA-4和HLA-G的表达与对照组没有显著的统计学差异(t=0.108,P=0.918 6;t=0.439,P=0.682 8);ELISA的结果显示相对于对照组,PP14组Treg细胞培养上清中IL-10和TGF-β的浓度分别上升了3.66倍和3.86倍(t=6.817,P=0.002 4;t=7.537,P=0.001 7);共培养实验显示PP14能够增强Treg细胞诱导Tfr细胞比例的增加,相对于共培养组,PP14组Tfr细胞比例增加了2.71倍(t=4.815,P=0.008 6),IL-10和TGF-β的阻断均能部分阻断这种增强作用(t=4.868,P=0.008 2;t=3.670,P=0.021 4)。结论:PP14能够通过分泌IL-10和TGF-β,显著增强Treg细胞诱导Tfr细胞比例的增加,这为不明原因复发性流产的治疗提供了一个新的靶点。
Objective:To investigate the effect and mechanism of placental protein 14(PP14) on the proliferation of follicular regulatory T cells( Tfr cells) induced by regulatory T cells( Treg cells). Methods: The lymphocytes in the peripheral blood of the healthy volunteers were separated,and the magnetic beads were selected to separate the Treg cells from the lymphocytes. The ratio of CD4+CD25+Foxp3+Treg cells and the expression of CTLA-4 and HLA-G on their surface were detected by flow cytometry,and the concentration of IL-10 and TGF-β in the supernatant was detected by ELISA. The co-culture experiment of Treg cells and lymphocytes was carried out in the Transwell,and the proportion of CD4+CXCR5+Foxp3+Tfr cells in lymphocytes was detected by flow cytometry. Results:Compared with the control group,the proportion of Treg cells in PP14 group increased by 1. 26 times( t = 4. 748,P = 0. 009 0),while the expression of CTLA-4 and HLA-G on their surface was not significantly different( t = 0. 108,P = 0. 918 6,t =0. 439,P = 0. 682 8). The results of ELISA showed that the concentration of IL-10 and TGF-β increased by 3. 66 times and 3. 86 times(t= 6. 817,P= 0. 002 4,t= 7. 537,P= 0. 001 7) in PP14 cell Treg supernatant,respectively. Co-culture experiments showed that PP14 could enhance the proliferation of Tfr cells induced by Treg cells,compared with the co-cultured group,the proportion of Tfr cells in PP14 group increased by 2. 71 times( t = 4. 815,P = 0. 008 6),blocking IL-10 and TGF-β could partially block this enhancement( t =4. 868 P = 0. 008 2; t = 3. 670,P = 0. 021 4). Conclusion:PP14 can significantly enhance the proliferation of Tfr cells induced by Treg cells,which provides a new target for the treatment of unexplained recurrent spontaneous abortion.
作者
林丽慧
陈瑾
唐梅
LIN Li-Hui;CHEN Jin;TANG Mei(Department of Gynaecology and Obstetrics,Hainan West Central Hospital,Danzhou 571700,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2018年第7期1075-1078,共4页
Chinese Journal of Immunology
关键词
胎盘蛋白14
调节性T细胞
滤泡调节性T细胞
不明原因复发性流产
Placental protein 14
Regulatory T cells
Follicular regulatory T cells
Unexplained recurrent spontaneous abortion