Ganesh Anupama, Lemongello Donna, Lee Evelyn, Peterson Julia, McLaughlin Bridget E, Ferre April L, Gillespie Geraldine M, Fuchs Dietmar, Deeks Steven G, Hunt Peter W, Price Richard W, Spudich Serena S, Shacklett Barbara L
1 Department of Medical Microbiology and Immunology, University of California , Davis, Davis, California.
2 Department of Neurology, San Francisco General Hospital, University of California , San Francisco, San Francisco, California.
AIDS Res Hum Retroviruses. 2016 Aug;32(8):791-800. doi: 10.1089/AID.2015.0313. Epub 2016 May 2.
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/μl. 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.
中枢神经系统（CNS）是HIV的重要靶标，脑脊液（CSF）可为了解中枢神经系统内宿主与病毒的相互作用提供一个窗口。本研究的目的是确定在未经抗逆转录病毒治疗（ART）的情况下维持低水平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。从11名HC中采集脑脊液和血液样本，这些HC根据血浆病毒载量（VL）持续低于2000拷贝/ml且未接受ART来定义。其中包括9名精英控制者（EC，血浆VL <40拷贝/ml）和2名病毒血症控制者（VC，VL为40 - 2000拷贝/ml）。所有控制者的脑脊液VL均<40拷贝/ml。还采集了三个比较组的样本：6名HIV非控制者（NC，VL >10000拷贝/ml，未接受ART）；7名因接受ART而病毒血症得到抑制的个体（Tx，VL <40拷贝/ml）；以及9名HIV阴性对照者。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的表达、活化标志物CD38和HLA - DR以及记忆/效应标志物CD45RA和CCR7。通过主要组织相容性复合体I类多聚体染色对HIV特异性CD8(+) T细胞进行定量。在体外以相似频率在HC和非控制者的脑脊液中检测到HIV特异性CD8(+) T细胞；最高频率出现在CD4计数低于500个细胞/μl的个体中。脑脊液中大多数HIV特异性CD8(+) T细胞是表达CCR5的效应记忆细胞。在脑脊液中检测到这些细胞表明HIV特异性T细胞对中枢神经系统区域进行了主动监测，包括在未经治疗的情况下长期控制HIV感染的个体中。
