Regulatory T cell frequencies do not correlate with breadth or magnitude of HIV-1-specific T cell responses.
Regulatory T cell frequencies do not correlate with breadth or magnitude of HIV-1-specific T cell responses.
复制标题
调节性 T 细胞频率与 HIV-1 特异性 T 细胞反应的广度或强度无关。
DOI：
10.1089/aid.2011.0353
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发表时间：
2012
影响因子：
1.5
通讯作者：
Addo,MarylynM
中科院分区：
文献类型：
--
作者：
Angin,Mathieu;Streeck,Hendrik;Wen,Fang;King,Melanie;Pereyra,Florencia;Altfeld,Marcus;Walker,BruceD;Addo,MarylynM
编者：尽管对HIV-1感染中的调节性T细胞（Tcells）进行了大量研究，但其在HIV-1发病机制中的作用尚未完全阐明。虽然有证据支持Tlethal通过影响HIV-1相关免疫激活1和最近的病毒复制2而产生有益作用，但其他数据表明，Tlethal通过抑制关键的病毒特异性免疫应答而产生负面作用。3，4 Tcl 3已显示在体外抑制HIV-1特异性效应子功能5，6，并且在疫苗研究中Tcl 3的消耗导致在针对癌症7和传染性病原体的疫苗设置中抗原特异性T细胞应答的可测量的增加。8然而，迄今为止，尚未研究Tclase在表位水平上对总HIV-1特异性CD 8 + T细胞应答的离体宽度和幅度的影响。对不同HIV-1感染个体队列中HIV-1特异性T细胞应答的综合分析报告了HIV-1特异性CD 8 + T细胞应答的宽度和幅度的广泛异质性，即使在HIV-1病毒载量均匀不可检测的个体中，如HIV“精英控制者”。9，10在这种情况下，我们假设Treg频率升高可能会影响总HIV-1特异性T细胞应答的离体宽度和幅度，这是当前研究之前尚未回答的研究问题。为了解决这个问题，我们测量了44名未经治疗的HIV-1感染者外周血单核细胞（PBMC）中CD 4 + CD 25 + FOXP 3+调节性T细胞的频率，其中包括18名HIV-1精英控制者[HIV-1病毒载量（VL）< 50 HIV-RNA拷贝/ml;中位数CD 4计数849个细胞/ml，IQR：686-1209）]，21例慢性未经治疗的HIV-1感染者（中位VL 44，500 HIV-RNA拷贝/ml，IQR：11，300 - 69，150;中位CD 4计数430个细胞/ml，IQR：353-547）和5例未经治疗的急性感染（中位VL 416，000 HIV-RNA拷贝/ml，IQR：228，500 - 1，613，000;中位CD 4计数480个细胞/ml，IQR：263-487）[设门方案图1a，使用适当的CD 25和FOXP 3荧光减一（FMO）对照来定义CD 25 + FOXP 3+群体]。我们同时筛选这些研究受试者的HIV-1特异性CD 8 + T细胞反应，使用一组222个HIV-1最佳表位肽，在IFN-c-ELISpot测定中针对患者的HLA-I类类型进行定制。
Editor: Despite significant research conducted on regulatory T cells (Tregs) in HIV-1 infection, their role in HIV-1 pathogenesis is not fully elucidated. While there is evidence to support a beneficial effect of Tregs through impact on HIV-1-associated immune activation1 and more recently viral replication, 2 other data suggest a negative effect via suppression of critical virus-specific immune responses. 3, 4 Tregs have been shown to suppress HIV-1-specific effector functions in vitro5, 6 and depletion of Tregs in vaccine studies lead to measurable increases in antigen-specific T cell responses in vaccine settings for cancer7 and infectious pathogens. 8 However, the impact of Tregs on ex vivo breadth and magnitude of the total HIV-1-specific CD8+ T cell response at the epitope level has not been investigated to date.Comprehensive analyses of HIV-1-specific T cell responses in different cohorts of HIV-1-infected individuals have reported extensive heterogeneity in breadth and magnitude of HIV-1-specific CD8+ T cell responses, even in individuals with uniformly undetectable HIV-1 viral load such as HIV ‘‘elite controllers.’’9, 10 In this context we hypothesized that elevated Treg frequencies may impact the ex vivo breadth and magnitude of the total HIV-1-specific T cell response, a research question unanswered prior to the current study. To address this question we measured the frequency of CD4+ CD25+ FOXP3+ regulatory T cells in peripheral blood mononuclear cells (PBMCs) from 44 untreated HIV-1-infected individuals, including 18 HIV-1 elite controllers [HIV-1 viral load (VL)< 50 HIV-RNA copies/ml; median CD4 count 849 cells/ll, IQR: 686–1209)], 21 individuals with chronic untreated HIV-1 infection (median VL 44,500 HIV-RNA copies/ml, IQR: 11,300–69,150; median CD4 count 430 cells/ll, IQR: 353–547), and 5 individuals with untreated acute infection (median VL 416,000 HIV-RNA copies/ml, IQR: 228,500–1,613,000; median CD4 count 480 cells/ll, IQR: 263–487)[gating scheme Fig. 1a, appropriate CD25 and FOXP3 Fluorescence Minus One (FMO) controls were used to define the CD25+ FOXP3+ population]. We concomitantly screened these study subjects for HIV-1-specific CD8+ T cell responses using a panel of 222 HIV-1 optimal epitope peptides tailored to the patients’ HLA-Class-I type in an IFN-c-ELISpot assay.