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CD4 弱表达 CD8 bright T 细胞与 HIV 感染者的神经炎症标志物呈负相关。

CD4 dim CD8 bright T cells are inversely associated with neuro-inflammatory markers among people with HIV.

机构信息

Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.

Department of Biology, College of Science, Jouf University, Sakaka, Aljouf, Saudi Arabia.

出版信息

AIDS. 2024 Jan 1;38(1):1-7. doi: 10.1097/QAD.0000000000003743. Epub 2023 Oct 3.

Abstract

OBJECTIVE

HIV-associated neuroinflammation persists in the brain despite suppressive combination antiretroviral therapy (cART). We evaluated associations between a subset of CD8 + T cells, termed CD4 dim CD8 bright T cells, and soluble markers of immune activation and/or neuroinflammation in the cerebrospinal fluid (CSF) and plasma of people with HIV (PWH).

DESIGN

Fifteen cART-naive PWH were enrolled and underwent blood draw, lumbar puncture for CSF collection, and neuropsychological tests at week 0 (pre-cART) and 24 weeks after cART initiation.

METHODS

CSF and peripheral blood T cells were evaluated with flow cytometry and soluble markers of immune activation were measured by multiplex and singleplex assays. Spearman bootstrap correlation coefficients with 10 000 resamples were computed and reported with corresponding 95% confidence intervals (CIs) for each marker of interest and T-cell type.

RESULTS

The frequency of CSF CD4 dim CD8 bright T cells at week 0 was inversely related with CSF neopterin. In contrast, at week 24, CSF CD4 - CD8 + T cells were positively correlated with CSF s100β, a marker of brain injury. In the blood, at week 0, CD4 dim CD8 bright T cells were inversely correlated with MCP-1, IP-10, IL-8, IL-6, G-CSF, and APRIL and positively correlated with plasma RANTES and MMP1. At week 0, the frequency of blood CD4 - CD8 + were positively correlated with CRP and BAFF.

CONCLUSION

CD4 dim CD8 bright T cells are associated with some anti-inflammatory properties, whereas CD4 - CD8 + T cells may contribute to inflammation and injury. Assessing the contrast between these two cell populations in neuroHIV may inform targeted therapeutic intervention to reduce neuroinflammation and associated neurocognitive impairment.

摘要

目的

尽管联合抗逆转录病毒疗法(cART)具有抑制作用,但 HIV 相关的神经炎症仍会在大脑中持续存在。我们评估了 HIV 感染者(PWH)脑脊液(CSF)和血浆中一组称为 CD4dimCD8brightT 细胞的 CD8+T 细胞亚群与免疫激活和/或神经炎症的可溶性标志物之间的关系。

设计

15 名未经 cART 治疗的 PWH 入组,并在 cART 开始前 0 周(cART 前)和 24 周后进行血液采集、腰椎穿刺采集 CSF 和神经心理学测试。

方法

使用流式细胞术评估 CSF 和外周血 T 细胞,并用多重和单重测定法测量免疫激活的可溶性标志物。计算了每个感兴趣的标志物和 T 细胞类型的 10000 个样本的 Spearman 自举相关系数,并报告了相应的 95%置信区间(CI)。

结果

第 0 周 CSF CD4dimCD8brightT 细胞的频率与 CSF 新蝶呤呈负相关。相反,第 24 周 CSF CD4-CD8+T 细胞与 CSF s100β呈正相关,后者是脑损伤的标志物。在血液中,第 0 周 CD4dimCD8brightT 细胞与 MCP-1、IP-10、IL-8、IL-6、G-CSF 和 APRIL 呈负相关,与血浆 RANTES 和 MMP1 呈正相关。第 0 周时,血液中 CD4-CD8+的频率与 CRP 和 BAFF 呈正相关。

结论

CD4dimCD8brightT 细胞与一些抗炎特性相关,而 CD4-CD8+T 细胞可能导致炎症和损伤。评估神经 HIV 中这两种细胞群之间的差异可能为减少神经炎症和相关的神经认知障碍提供靶向治疗干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4c0/10715695/d17c7cac54c6/aids-38-001-g001.jpg

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