HIV-1感染者CD4＾＋T细胞受体基因多样性特点及其与病毒载量的相关性  

Association of T cell receptor diversity of CD4 ^＋ T lymphocytes with viral load in individuals with HIV-1infection

作　　者：高占[2] 任国良[1] 宋玉国[2] 贾明明[1] 郑扬[1] 赵全壁[1] 邵一鸣 毕胜利[2] 洪坤学[1] 

机构地区：[1]中国疾病预防控制中心性病艾滋病预防控制中心传染病预防控制国家重点实验室,北京102206 [2]北华大学医学部,132011

出　　处：《中华微生物学和免疫学杂志》2011年第5期385-389,共5页Chinese Journal of Microbiology and Immunology

基　　金：“十一五”重大传染病防治研究项目（2008ZX10001.010）;973项目（2006CB504207）

摘　　要：目的分析HIV-1感染者CD4^＋T细胞受体（TCR）基因的多样性特征及其与病毒载量的相关性。方法应用抗CD4单克隆抗体从25份HIV-1感染者和10份HIV-1阴性对照样本外周血单个核细胞（PBMC）中分离CD4^＋T细胞，提取细胞总RNA，然后通过逆转录及巢式多聚酶链反应（nested-PCR）对TCR22个vβ基因家族的互补决定区3（CDR3）进行扩增，利用AB13700测序仪对扩增的PCR产物进行扫描，定量分析HIV-1感染者TCRCDR3区多样性变化特征及其与病毒载量的相关性。结果HIV-1感染者CIM^＋T细胞TCRCDR3区平均D（distance）值显著高于正常对照组（P〈0．05），TCR Vβ基因各家族CDR3长度谱型成寡克隆分布，TCRCDR3区的紊乱与病毒载量呈正相关（r=0．494，P〈0．05）；HIV-l感染引起TCR多样性的改变不仅表现在不同vβ基因家族上，而且也表现在CDR3长度上，其中感染者VB8、V1322、Vβ23基因家族的变化与正常人差异有统计学意义。结论HIV-1感染能引起CD4^＋T细胞TCR基因多样性的减少及高斯（Gaussian）分布的破坏，TCRCDR3区的紊乱与病毒载量呈正相关。Objective To assess the impact of the virus on the complementary determining region 3 （CDR3） length diversity of T cell receptor（TCR） Vβ repertoires of CD4 ^＋T lymphocytes and to explore its association with viral load in individuals with HIV-1 infection. Methods The TCR repertoire was examined using spectratyping of CDR3 length diversity within CD4^＋ T cells in HIV infected and healthy adults. Separation of CD4^＋ T cells from peripheral blood mononuclear cells （PBMCs） was carried out by using immunomagnctic beads coated with anti-CD4 antibody. Total RNAs from the purified CD4 ^＋ T lympbocytes were isolated and used to perform nested-PCR amplifications in CDR3 of 22 TCR gene families. CDR3 diversity and its association with viral load in individuals with HIV-1 infection were analyzed. Results An average diversity for all CDR3 profiles in CD4 ^＋ T cells from 25 HIV-infected individuals was significantly different as compared to 10 age-matched healthy donors （P 〈 0.05 ） with the HIV-infected individuals losing diversity in the CDR3 profiles. There was positive correlation between changes in TCR CDR3 diversity and viral load （ r = 0.494, P 〈 0.05 ）. The changes in CDR3 length diversity of Vβfamilies in HIV-infected individuals, particular in Vβ8, Vβ22, Vβ23 were statistically different from the healthy controls. Conclusion HIV-1 infection might induce the loss of TCR Vβ repertoire diversity and disrupt the CDR3 Gaussian distributions within CD4 ＋ T cells. There should be positive correlation between changes in TCR CDR3 diversity and the viral load in HIV-1 infected patients.

关 键 词：CD4^+T淋巴细胞 HIV-1 T细胞受体 互补决定区3 

分 类 号：R51[医药卫生—内科学]