BM-MSCs延缓CD8^(+)初始T细胞衰老  

BM-MSCs delay the senescence of naive CD8^(+)T cells

作　　者：高竞溪 赵晓妍 朱星雨 孙昭[2] 韩钦[1] 赵春华[1] GAO Jingxi;ZHAO Xiaoyan;ZHU Xingyu;SUN Zhao;HAN Qin;ZHAO Chunhua(Center for Excellence in Tissue Engineering,Chinese Academy of Medical Sciences,Institute of Basic Medical Sciences CAMS,School of Basie Medicine PUMC,Beijing 100005;Department of Oncology,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China)

机构地区：[1]中国医学科学院基础医学研究所、北京协和医学院基础学院、中国医学科学院组织工程研究中心,北京100005 [2]中国医学科学院、北京协和医学院、北京协和医院肿瘤内科,北京100730

出　　处：《基础医学与临床》2024年第5期683-689,共7页Basic and Clinical Medicine

基　　金：中国医学科学院医学与健康科技创新工程(2022-I2M-1-012)。

摘　　要：目的验证骨髓间充质干细胞(BM-MSCs)缓解免疫衰老的作用,探究其衰老改善的主要免疫细胞群体。方法分离获得小鼠脾淋巴细胞,刺激增殖7d构建复制性衰老细胞模型。利用流式细胞测量术检测年轻对照组、复制性衰老对照组和BM-MSCs共培养组T细胞亚群衰老标志物p16ink4a(p16)和p21cip1(p21)的表达水平。结果T淋巴细胞复制性衰老模型中观察到持续增殖后CD8^(+)T细胞较CD4^(+)T细胞衰老显著,在CD8^(+)T细胞的初始细胞、效应细胞亚群中,效应细胞衰老最显著;BM-MSCs共培养对衰老的效应细胞没有明显影响,主要通过延缓初始T细胞的衰老,达到缓解CD8^(+)T细胞衰老的作用(P<0.01,P<0.001)。结论与BM-MSCs共培养可以缓解T细胞的复制性衰老表型,对CD8^(+)T细胞的抗衰作用更显著,主要通过抑制初始T细胞的衰老实现。Objective To verify the effect of bone marrow mesenchymal stem cells(BM-MSCs)in alleviating immune senescence,and to explore the main immune cell population improved by BM-MSCs.Methods Mouse spleen lymphocytes were isolated and stimulated to proliferate for 7 days for constructing a replicative aging model.Flow cytometry was used to detect the p16ink4a(p16)and p21cip1(p21)expression by T cell subpopulation in the young control group,the replicative senescence control group and the BM-MSCs co-cultured group.Results In the replicative senescence model of T lymphocytes,it was observed that CD8^(+)T cells senescent significantly as compared with CD4^(+)T cells after continuous proliferation.Among the naive cells and effector cell subsets of CD8^(+)T cells,effector cell senescence was the most significant.BM-MSCs co-culture had no significant effect on senescent effector cells,and mainly alleviated the senescence of CD8^(+)T cells by delaying the senescence of naive T cells(P<0.01,P<0.001).Conclusions BM-MSCs co-culture can alleviate the replicative senescence phenotype of T cells and has a more significant anti-senescence effect on CD8^(+)T cells by inhibiting the initial senescence of T cells as a major mechcanism.

关 键 词：骨髓间充质干细胞(BM-MSCs) T细胞衰老 延缓衰老 

分 类 号：Q291[生物学—细胞生物学]