Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected.

Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected.
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替代效应器功能分析可识别高度 HIV 暴露且未感染的个体中广泛的 HIV 特异性 T 细胞反应。

DOI:
10.1093/infdis/jiu534
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发表时间:
2015
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Korber,
Korber,
中科院分区:
--
文献类型:
--
作者:
Ruiz-Riol,Marta;Llano,Anuska;Ibarrondo,Javier;Zamarreño,Jennifer;Yusim,Karina;Bach,Vanessa;Mothe,Beatriz;Perez-Alvarez,Susana;Fernandez,MarcoA;Requena,Gerard;Meulbroek,Michael;Pujol,Ferran;Leon,Agathe;Cobarsi,Patricia;Korber,

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需要对HIV控制者和HIV高暴露但血清阴性个体(HESN)中对人类免疫缺陷病毒(HIV)的宿主免疫应答进行表征,以指导有效的预防和治疗候选疫苗的开发。然而,一些技术障碍严重限制了有效的病毒特异性T细胞应答的定义。通过使用一个toggle肽的方法,它考虑到艾滋病毒序列的多样性,和一种新的,加强细胞因子染色/流式细胞术的策略,我们在这里描述了新的模式的T细胞对艾滋病毒的反应,将错过标准检测。重要的是,这种方法还允许检测HESN个体中广泛和强烈的病毒特异性T细胞应答,其特征在于T辅助细胞1型白细胞介素样效应物谱,并产生与HIV感染的潜在控制相关的细胞因子,包括白细胞介素10,白细胞介素13和白细胞介素22。这些结果建立了一种新的方法,以提高目前对HIV特异性T细胞免疫的理解,并确定细胞免疫反应和单个细胞因子作为相对HIV抗性的潜在标志物。因此,这些发现也有助于开发类似的策略,以更全面地评估宿主对其他人类感染和免疫介导的疾病的免疫反应。
The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine–like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders.
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