High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
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DOI：
10.1097/qai.0000000000001301
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发表时间：
2017-05-01
影响因子：
3.6
通讯作者：
Trautmann, Lydie
中科院分区：
文献类型：
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作者：
Kessing, Cari F.;Spudich, Serena;Trautmann, Lydie
背景：CD8(+) T细胞浸润中枢神经系统（CNS）与许多神经退行性疾病的神经炎症有关，包括hiv相关痴呆。然而，CD8(+) T细胞在急性HIV感染（AHI）期间在中枢神经系统中的作用尚不清楚。方法：我们分析了在AHI （n = 26）、慢性（n = 23）和未感染（n = 8）的早期阶段捕获的一个独特队列脑脊液（CSF）中CD8(+) T细胞的表型、基因表达、T细胞受体（TCR）库和HIV特异性。结果：与未感染的对照组相比，AHI患者CSF CD8(+) T细胞升高。激活的CSF CD8(+) T细胞的频率与CSF HIV RNA和CNS炎症标志物呈正相关。相比之下，慢性HIV感染期间激活的CSF CD8(+) T细胞与神经损伤和小胶质细胞激活的标志物相关。AHI患者的CSF CD8(+) T细胞表现出与CD8(+) T细胞效应功能、增殖和TCR信号相关的功能性基因表达谱增加，这是一种独特的限制性TCR Vbeta库，与周围细胞相比，含有针对独特HIV表位的HIV特异性CD8(+) T细胞。结论：这些结果表明AHI中的CSF CD8(+) T细胞在中枢神经系统中扩增是功能性的，并且针对HIV抗原。因此，如果早期开始联合抗逆转录病毒治疗，这些细胞可以在慢性HIV感染中发挥有益的保护作用。
Background: Central nervous system (CNS) infiltration by CD8(+) T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8(+) T cells in the CNS during acute HIV infection (AHI) is unknown.Methods: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8(+) T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8).Results: CSF CD8(+) T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8(+) T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8(+) T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8(+) T cells in AHI exhibited increased functional gene expression profiles associated with CD8(+) T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8(+) T cells directed to unique HIV epitopes compared with the periphery.Conclusions: These results suggest that CSF CD8(+) T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.