IFN-γ对人胎盘源间充质干细胞上PDL2表达及诱导外周血CD8^＋IL-10^＋T细胞亚群分化的调节作用  

Regulatory effects of IFN-γon the expression of PDL2 on human placenta mesenchymal stem cells （hPMSCs） and the hPMSCs-induced differentiation of peripheral blood CD8＋IL-10＋T cell subsets

作　　者：李恒[1] 王国艳[1] 王炜玮[1] 王斐斐[1] 刘冉冉[2] 栾希英[1] 

机构地区：[1]滨州医学院免疫教研室,烟台264003 [2]滨州医学院组胚教研室,烟台264003

出　　处：《中华微生物学和免疫学杂志》2014年第9期691-696,共6页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金（31370905）

摘　　要：目的：探讨IFN-γ对人胎盘源间充质干细胞（humanplacentamesenchymalstemcells，hPMSCs）上程序性死亡配体2（programmeddeathligand2，PDL2）的表达及诱导外周血CD8＋IL-10＋T细胞亚群分化的调节作用。方法应用酶消化法分离hPMSCs；RT-PCR和FCM分析hPMSCs上PDL2的表达，以及IFN-γ对PDL2表达的影响；Ficoll密度梯度离心法分离健康人外周血单个核细胞（PBMC），并用E花环法纯化T细胞；FCM分别检测PDL2单克隆抗体（McAb）阻断及IFN-γ刺激条件下，hPMSCs对PHA和CD3/CD28McAb活化的T细胞中CD8＋IL-10＋T细胞亚群变化。结果hPMSCs高表达PDL2，IFN-γ能够上调hPMSCs上PDL2的表达；FCM分析结果显示，hPMSCs可诱导CD8＋IL-10＋T细胞亚群的分化，在PHA和CD3/CD28McAb活化条件下，外周血T细胞中CD8＋IL-10＋T细胞亚群比例在有hPMSCs存在组明显高于无hPMSCs存在组（P＜0．01）；阻断PDL2的表达后，hPMSCs对T细胞向CD8＋IL-10＋T细胞亚群诱导分化能力明显下降；IFN-γ刺激后的hPMSCs对外周血中CD8＋IL-10＋T细胞亚群的诱导作用明显上调。结论hPMSCs能够诱导外周血中T细胞向CD8＋IL-10＋T细胞亚群分化，PDL2能够协同hPMSCs诱导CD8＋IL-10＋T细胞亚群形成；IFN-γ通过上调hPMSCs对PDL2的表达，促进hPMSCs对外周血T细胞向CD8＋IL-10＋T细胞亚群转化的调节作用。Objective To investigate the regulatory effects of IFN-γon the expression of pro-grammed death ligand 2 （PDL2） on human placenta mesenchymal stem cells （hPMSCs） and the hPMSCs-induced differentiation of peripheral blood CD 8＋IL-10＋T cell subsets .Methods hPMSCs were isolated from mature human placenta by enzyme digestion .The expression of PDL2 on hPMSCs and the regulatory effects of IFN-γon PDL2 expression were detected by RT-PCR and flow cytometry （ FCM ） , respectively . Peripheral blood mononuclear cells （PBMCs） were isolated from healthy subjects by density gradient centrif-ugation.T cells were purified with sheep red blood cells .FCM was used to detect the ratios of CD 8＋IL-10＋T cell subsets in PHA or CD3/CD28 beads activated T cells in the presence of hPMSCs treated with Anti-PDL2 McAb or IFN-γ.Results PDL2 molecules were highly expressed on hPMSCs that could be further enhanced by IFN-γ.The results of FCM demonstrated that hPMSCs could induce the differentiation of CD 8＋IL-10＋T cell subsets .The ratios of CD8＋IL-10＋T cell population in T cells activated by different stimulators including PHA and CD3/CD28 beads were significantly increased in the presence of hPMSCs as compared with those without hPMSCs （P〈0.01）.In addition, the antibody blocking experiments indicated that PDL 2 McAb down-regulated the percentages of CD 8＋IL-10＋T cell subsets in PHA or CD 3/CD28 beads stimulated T cells in the presence of hPMSCs as compared with those of unblocked groups .CD8＋IL-10＋T cell subsets were up-regulated in IFN-γtreated hPMSCs groups as compared with those of untreated groups .Conclusion hPMSCs could induce the differentiation of peripheral blood T cells into CD 8＋IL-10＋T cell subsets , which was enhanced by PDL 2 expressed on hPMSCs .IFN-γcould promote the differentiation of CD 8＋IL-10＋T cell subsets induced by hPMSCs through up-regulating the expression of PDL2 on hPMSCs.

关 键 词：胎盘间充质干细胞 PDL2 CD8^+IL-10^+T细胞 IFN-Γ 

分 类 号：R392[医药卫生—免疫学]