Persistent T Cell Repertoire Perturbation and T Cell Activation in HIV After Long Term Treatment.
Persistent T Cell Repertoire Perturbation and T Cell Activation in HIV After Long Term Treatment.
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HIV长期治疗后T细胞库持续紊乱和T细胞活化
DOI：
10.3389/fimmu.2021.634489
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发表时间：
2021
影响因子：
7.3
通讯作者：
Noursadeghi M
中科院分区：
文献类型：
--
作者：
Turner CT;Brown J;Shaw E;Uddin I;Tsaliki E;Roe JK;Pollara G;Sun Y;Heather JM;Lipman M;Chain B;Noursadeghi M
在艾滋病毒感染者（PLHIV）中，我们试图验证长期抗逆转录病毒治疗恢复正常T细胞库的假设，并研究残留库异常与持续免疫系统失调的功能关系。我们在PLHIV和HIV阴性志愿者中进行了一项病例对照研究，通过RNA测序对循环T细胞受体库和全血转录组进行了研究，并辅以常规收集的医疗记录元数据。T细胞受体测序显示PLHIV的克隆T细胞库持续异常，其特征在于库多样性降低和寡克隆T细胞扩增与CD8 T细胞计数升高相关。我们没有发现证据表明这些扩增是由巨细胞病毒或其他常见抗原驱动的。扩增克隆中长CDR3序列的频率增加和公共序列的频率减少暗示异常胸腺选择是一个促成因素。库中的这些异常与全基因组血液转录组中持续T细胞活化的系统水平证据相关。在长期抗逆转录病毒治疗的PLHIV中，T细胞受体库的多样性仍然显著减少，并被特异性克隆所扭曲，部分原因是胸腺输出改变，并与T细胞介导的慢性免疫激活相关。进一步研究胸腺功能和T细胞克隆选择的抗原驱动因素对完全重建正常免疫功能至关重要。
In people living with HIV (PLHIV), we sought to test the hypothesis that long term anti-retroviral therapy restores the normal T cell repertoire, and investigate the functional relationship of residual repertoire abnormalities to persistent immune system dysregulation. We conducted a case-control study in PLHIV and HIV-negative volunteers, of circulating T cell receptor repertoires and whole blood transcriptomes by RNA sequencing, complemented by metadata from routinely collected health care records. T cell receptor sequencing revealed persistent abnormalities in the clonal T cell repertoire of PLHIV, characterized by reduced repertoire diversity and oligoclonal T cell expansion correlated with elevated CD8 T cell counts. We found no evidence that these expansions were driven by cytomegalovirus or another common antigen. Increased frequency of long CDR3 sequences and reduced frequency of public sequences among the expanded clones implicated abnormal thymic selection as a contributing factor. These abnormalities in the repertoire correlated with systems level evidence of persistent T cell activation in genome-wide blood transcriptomes. The diversity of T cell receptor repertoires in PLHIV on long term anti-retroviral therapy remains significantly depleted, and skewed by idiosyncratic clones, partly attributable to altered thymic output and associated with T cell mediated chronic immune activation. Further investigation of thymic function and the antigenic drivers of T cell clonal selection in PLHIV are critical to efforts to fully re-establish normal immune function.
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影响因子：
30.8
作者：
Emerson, Ryan O.;DeWitt, William S.;Robins, Harlan S.
通讯作者：
Robins, Harlan S.
DOI：
10.1086/597476
发表时间：
2009-04-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Jiang W;Lederman MM;Hunt P;Sieg SF;Haley K;Rodriguez B;Landay A;Martin J;Sinclair E;Asher AI;Deeks SG;Douek DC;Brenchley JM
通讯作者：
Brenchley JM
影响因子：
5.1
作者：
Frazier, Emma L.;Sutton, Madeline Y.;Weiser, John
通讯作者：
Weiser, John
XGR软件可增强对基因组摘要数据的解释，并通过应用于免疫特征说明。
影响因子：
12.3
作者：
Fang H;Knezevic B;Burnham KL;Knight JC
通讯作者：
Knight JC
影响因子：
3.5
作者：
Herdman, M.;Gudex, C.;Lloyd, A.;Janssen, M. F.;Kind, P.;Parkin, D.;Bonsel, G.;Badia, X.
通讯作者：
Badia, X.