中国恒河猴感染SIV后T淋巴细胞初始、记忆亚群的变化  

Dynamics of T-cell memory subtypes in SIV infected Chinese rhesus monkeys

作　　者：陈颂[1] 吴小闲[2] 卢耀增[2] 潘菊华[3] 王阶[3] 黄世敬[3] 赖春辉[1] 郭卫中[1] 孙丽华[2] 鲍琳琳[2] 卢葳[4,1] 

机构地区：[1]广州中医药大学热带医学研究所,广州510405 [2]中国医学科学院&北京协和医学院医学实验动物研究所,北京100021 [3]中国中医科学院广安门医院,北京100053 [4]法国发展研究院-UMI233中国部

出　　处：《中国免疫学杂志》2012年第6期483-488,共6页Chinese Journal of Immunology

基　　金：国家科技重大专项(No.2008ZX10005-004)项目资助

摘　　要：目的:对中国恒河猴感染猴免疫缺陷病毒(SIV)后CD4T初始、记忆亚群的细胞进行分析,了解各亚群的变化规律以及在AIDS发病过程中的意义。方法:使用SIVmac239毒株感染20只中国恒河猴,观察18个月;在感染前、后各时间点,使用实时荧光定量PCR(TaqMan探针法)进行病毒载量的检测;使用CD3/CD4/CD28/CD95表面标记的组合,进行CD4及其初始/记忆亚群比例的流式分析,并结合血常规检测的结果计算CD4及其各亚群的绝对数。结果:得到了CD4各个亚群在SIV感染后的变化曲线;并发现SIV感染后CD4减少的主体是中央型记忆(CM)CD4+T细胞;而初始型CD4+T在半数动物逐渐缓慢减少,但个体间差异较大。此外,还发现快速进展型RM449猴在死亡前其初始型及CM CD4仍较高,但其初始型CD4细胞在流式图上存在着类似"转化阻滞"的现象。结论:本研究展示了CD4细胞的初始、记忆亚群在感染SIV后的变化规律;对其进行细分研究,有助于更准确地了解体内免疫状态的变化,为临床疗效观察、免疫状态评估等提供参考。Objective： To explore the dynamics of T-cell nave/memory subsets in SIV infected Chinese rhesus monkeys. Methods：20 Chinese rhesus monkeys were infected by SIVmac239,and their plasma viral load were determined by quantitative Taqman real-time RT-PCR analysis within a follow-up period of 18 months.Moreover,proportions of their CD4＋ T cells and its nave/memory subsets were analyzed by flow cytometry using a combination of surface markers CD3/CD4/CD28/CD95,by which the absolute cell counts of CD4 and its subsets were also computed based on the routine blood tests. Results： Dynamics of the T-cell nave/memory subsets including their percentages and absolute counts were illustrated.Moreover,central memory CD4 showed to be the majority of cell-loss after SIV infection,which decreased more significantly and accordantly than total CD4,and should be further evaluated as a better indicator for clinical surveillance and drugs judgement.Nave CD4 T cell also decreased gradually with disease progression in half of these animals with more variation among individuals.But impressively,1 monkey（RM449） with rapidly disease progression died with relatively higher nave and central memory CD4＋ T cells,which may be partially explained by the blockage of nave CD4 differentiation into effector memory CD4,as revealed by the flow cytometry assay. Conclusion： The dynamics of different subsets of CD4 T cells in Chinese rhesus monkeys infected with SIVmac239 were surveyed.These data are necessary for the further research of cellular anti-SIV immunity,and may be useful for the clinical judgement of immune reconstitution and vaccine evaluation in HIV/AIDS research.

关 键 词：猴免疫缺陷病毒 中国恒河猴 T细胞 记忆细胞亚群 

分 类 号：R392.12[医药卫生—免疫学]