Department of Neurology, University Hospital of Muenster Albert-Schweitzer-Campus 1, D-48149, Muenster, Germany.
Department of Internal Medicine D, University Hospital of Muenster Albert-Schweitzer-Campus 1, D-48149, Muenster, Germany.
Ann Clin Transl Neurol. 2015 Sep;2(9):906-19. doi: 10.1002/acn3.227. Epub 2015 Aug 18.
HIV-associated neurocognitive disorders (HAND) remain a challenge despite combination antiretroviral therapy (cART). Immune cell activation has been implicated to play a major role in the development of HAND.
In this study, we used multicolor flow cytometry on peripheral blood (PB) and cerebrospinal fluid (CSF) samples to determine the expression of HLA-DR and programmed death-1 (PD-1) on CD4+ and CD8+ T cells in patients with chronic HIV infection. Expression levels were correlated with HI virus load in PB and CSF, classification of HAND and severity of magnetic resonance imaging (MRI) signal abnormalities.
In a cohort of 86 HIV patients we found that the grade of neurocognitive impairment and the severity of MRI signal abnormalities correlated with decreasing CD4/CD8-ratios and increased frequencies of HLA-DR expressing CD4+ and CD8+ T cells reaching the highest values in the CSF samples. Importantly, HLA-DR upregulation was still detectable in virologically suppressed HIV patients. Further, T-cell subpopulation analysis of 40 HIV patients showed a significant shift from naïve to effector memory (EM) T cells that was negatively correlated with the grade of neurocognitive impairment in the PB samples. Moreover, PD-1 was significantly increased on CD4+ memory T cells with highest levels on EM T cells in HIV patients with mild or severe neurocognitive alterations.
The CD4/CD8 ratio, the proportion of EM to naïve T cells and the immune activation profile of CD4+ and CD8+ T cells in PB and CSF might be useful parameters to monitor the efficacy of cART and to identify HIV patients at risk of further neurocognitive deterioration.
尽管联合抗逆转录病毒疗法（cART）已得到广泛应用，但与 HIV 相关的神经认知障碍（HAND）仍然是一个挑战。免疫细胞的激活被认为在 HAND 的发展中起主要作用。
在这项研究中，我们使用多色流式细胞术检测慢性 HIV 感染患者外周血（PB）和脑脊液（CSF）样本中 CD4+和 CD8+T 细胞上 HLA-DR 和程序性死亡受体-1（PD-1）的表达。表达水平与 PB 和 CSF 中的 HI 病毒载量、HAND 的分类以及磁共振成像（MRI）信号异常的严重程度相关。
在 86 名 HIV 患者的队列中，我们发现神经认知障碍的严重程度和 MRI 信号异常的严重程度与 CD4/CD8 比值的降低以及 HLA-DR 表达的 CD4+和 CD8+T 细胞频率的增加相关，这些频率在 CSF 样本中达到最高值。重要的是，在病毒学抑制的 HIV 患者中仍可检测到 HLA-DR 的上调。此外，对 40 名 HIV 患者的 T 细胞亚群分析显示，从幼稚到效应记忆（EM）T 细胞的显著转变与 PB 样本中的神经认知障碍严重程度呈负相关。此外，在 HIV 患者中，PD-1 在 CD4+记忆 T 细胞上显著增加，在 EM T 细胞上的水平最高，并且与轻度或重度神经认知改变的患者相关。
PB 和 CSF 中 CD4/CD8 比值、EM 与幼稚 T 细胞的比例以及 CD4+和 CD8+T 细胞的免疫激活谱可能是监测 cART 疗效和识别有进一步神经认知恶化风险的 HIV 患者的有用参数。
