HIV感染对机体MDSC细胞分化及其免疫抑制功能的影响  

Impact of HIV infection on differentiation of MDSC and its immune suppressive function

作　　者：李文博[1] 任伟宏[2] 桑锋[2] 李延卿[2] 冯倩[2] 冯慧洁[1] 

机构地区：[1]河南中医学院,郑州450000 [2]河南中医学院第一附属医院检验科中医药防治艾滋病重点实验室,郑州450000

出　　处：《现代免疫学》2016年第2期99-103,共5页Current Immunology

基　　金：河南省教育厅自然科学研究基金(13A360564);河南中医学院研究生创新基金

摘　　要：骨髓源性抑制细胞是一群具有免疫抑制作用的异质性细胞,HIV感染后的机体免疫系统异常调节可能与MDSC有关。因此,我们采用流式细胞分析检测HIV感染者及健康人群外周血MDSC亚群及细胞内精氨酸酶(Arg1)的表达,分析比较MDSC亚群及细胞内Arg1在以上两组间的差异;并通过HIV感染者血清与健康人外周血单个核细胞体外共培养方法,5d后观察HIV感染者血清对健康人MDSC的诱导与分化;采用免疫磁珠分选的方法分选HIV阳性血清诱导的MDSC,与CFSE标记的CD8+T淋巴细胞以2∶1的比例在CD3/CD28免疫磁珠的诱导下体外共培养3d,流式细胞仪检测共培养前后CD8^+T淋巴细胞在培养体系所占比例及CFSE荧光强度的改变。结果显示,与健康人外周血MDSC亚群比较,HIV感染者Lin^-HLA-DR^-CD33^+CD11b^+CD14^+标记的M-MDSC有显著统计学差异(P=0.01);HIV感染者M-MDSC细胞内Arg1的水平呈现高表达(23.1±9.3)%,与G-MDSC细胞内Arg1的水平比较(4.7±1.3)%,具有显著性差异(P=0.00);HIV阳性血清与健康人单个核细胞共培养后,M-MDSC的亚群高于培养前(P=0.008);HIV诱导的MDSC与CFSE标记的CD8^+T淋巴细胞在CD3/CD28刺激后,CD8^+T淋巴细胞在培养体系中所占比例低于单纯的CD3/CD28诱导组(43.7%±6.7%,64.7%±8.2%;P<0.05),CFSE荧光强度的改变亦低于单纯的CD3/CD28诱导组。以上结果提示我们,HIV患者外周血MDSC亚群以M-MDSC为主;Arg1是M-MDSC发挥免疫抑制作用的重要途径;HIV阳性血清可诱导MDSC向M-MDSC方向分化,且HIV诱导后的MDSC抑制CD8^+T淋巴细胞的增殖。To investigate polarization of MDSCs and how it play immune-suppression role after HIV infection, we used tlow cy- tometry to draw a comparison of differences of MDSCs population and intracellular level of arginasel between individuals with HIV infection and healthy subjects. PBMC from healthy individuals were cultured in HIV positive serum for 5 days in vitro in order to determine the influence of HIV serum to MDSCs in terms of induction and differentiation of MDSC from healthy sub- jects. MDSCs that have been treated with HIV-containing serum were separated by using magnetic activated cell sorting , and co-cultured with CFSE-labelled CD8＋ T lymphocytes for 3 days in a ratio of 2 ： 1, CD8＋ T lymphocytes were subsequently ex- amined by flow cytometry for change of proportion of CD8＋ T cells as well CFSE intensity. The results showed that, compared with healthy individuals, Lin-HLA-DR-CD33＋ CD11b＋ CD14＋ in the infected individuals were significantly different from that from healthy individuals（P = 0.0 1）. In addition, levels of intracellular Argl of M-MDSC from the infected individuals were significantly increased as compared with those from G-MDSC（23.1%±9.3% vs 4.7%±1.3%, P = 0.00）. In conclu- sion, HIV-infected peripheral blood MDSCs subset is given priority to M-MDSCs, and arginasel avenue is a vital way for M- MDSCs to play immuno-suppression role. HIV positive serum can promote MDSCs polarization to M-MDSCs, and HIV-in- duced MDSCs can inhibit the proliferation of CD8＋ T lymphocytes.

关 键 词：HIV CD8+T淋巴细胞 MDSC Arg1 

分 类 号：R392.12[医药卫生—免疫学]