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首页> 外文期刊>AIDS Research and Human Retroviruses >Immune Activation and HIV-Specific CD8(+) T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers
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Immune Activation and HIV-Specific CD8(+) T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers

机译:免疫激活和艾滋病毒控制者和非控制者的脑脊液中的HIV特异性CD8(+)T细胞。

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摘要

The central nervous system (CNS) is an important target of HIV, and cerebrospinal fluid (CSF) can provide a window into host-virus interactions within the CNS. The goal of this study was to determine whether HIV-specific CD8(+) T cells are present in CSF of HIV controllers (HC), who maintain low to undetectable plasma viremia without antiretroviral therapy (ART). CSF and blood were sampled from 11 HC, defined based on plasma viral load (VL) consistently below 2,000 copies/ml without ART. These included nine elite controllers (EC, plasma VL < 40 copies/ml) and two viremic controllers (VC, VL 40-2,000 copies/ml). All controllers had CSF VL < 40 copies/ml. Three comparison groups were also sampled: six HIV noncontrollers (NC, VL > 10,000 copies/ml, no ART); seven individuals with viremia suppressed due to ART (Tx, VL < 40 copies/ml); and nine HIV-negative controls. CD4(+) and CD8(+) T cells in CSF and blood were analyzed by flow cytometry to assess expression of CCR5, activation markers CD38 and HLA-DR, and memory/effector markers CD45RA and CCR7. HIV-specific CD8(+) T cells were quantified by major histocompatibility complex class I multimer staining. HIV-specific CD8(+) T cells were detected ex vivo at similar frequencies in CSF of HC and noncontrollers; the highest frequencies were in individuals with CD4 counts below 500 cells/mu l. The majority of HIV-specific CD8(+) T cells in CSF were effector memory cells expressing CCR5. Detection of these cells in CSF suggests active surveillance of the CNS compartment by HIV-specific T cells, including in individuals with long-term control of HIV infection in the absence of therapy.
机译:中枢神经系统(CNS)是HIV的重要靶标,而脑脊液(CSF)可以为了解CNS中宿主与病毒之间的相互作用提供一个窗口。这项研究的目的是确定在没有抗逆转录病毒疗法(ART)的情况下,维持低至无法检测到的血浆病毒血症的HIV控制者(HC)的脑脊液中是否存在HIV特异性CD8(+)T细胞。 CSF和血液是从11 HC中取样的,根据血浆病毒载量(VL)定义,始终低于2,000拷贝/ ml,而无ART。这些包括九个精英控制器(EC,血浆VL <40拷贝/毫升)和两个病毒血症控制器(VC,VL 40-2,000拷贝/毫升)。所有控制者的CSF VL <40拷贝/ ml。还对三个对照组进行了采样:六个HIV非控制者(NC,VL> 10,000拷贝/ ml,无ART);七个因ART抑制病毒血症的个体(Tx,VL <40拷贝/ ml);以及九项HIV阴性对照。通过流式细胞术分析脑脊液和血液中的CD4(+)和CD8(+)T细胞,以评估CCR5,激活标记CD38和HLA-DR以及记忆/效应标记CD45RA和CCR7的表达。通过主要的组织相容性复合体I类多聚体染色对HIV特异性CD8(+)T细胞进行定量。在HC和非控制者的CSF中以相似的频率离体检测到HIV特异性CD8(+)T细胞。 CD4计数低于500个细胞/微升的个体出现频率最高。 CSF中大多数HIV特异性CD8(+)T细胞是表达CCR5的效应记忆细胞。对CSF中这些细胞的检测表明,HIV特异性T细胞可以对CNS隔室进行主动监视,包括在没有治疗的情况下可以长期控制HIV感染的个体。

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