CD57+ T cell transmigration through vascular endothelial cells is enhanced by TNF: A novel model of cardiovascular risk in people with HIV.

IF 1.5 4区 医学 Q4 IMMUNOLOGY AIDS research and human retroviruses Pub Date : 2024-09-18 DOI:10.1089/aid.2024.0057
Xi Su,Michael Freeman
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Abstract

People with human immunodeficiency virus (PWH), despite achieving viral suppression through antiretroviral therapy, face increased risk and earlier onset of atherosclerotic cardiovascular diseases than the general population. CD57+ T cells can be readily recovered from atherosclerotic plaques and likely contribute to disease by targeting endothelial cells (ECs), however the specific mechanisms facilitating the infiltration of these cells into plaques remain elusive. Here, we report the development of a novel assay to quantify T cell adhesion to and transmigration through a primary human vascular EC monolayer and show that CD57+ T cells preferentially adhere to and transmigrate through the monolayer. Moreover, activating the ECs with tumor necrosis factor (TNF) significantly increased the transmigration of CD57+ T cells, supporting a role for TNF in promoting the vascular homing of CD57+ T cells. This model will allow for elucidating the mechanisms of, and testing interventions to prevent, CD57+ T cell infiltration into plaques.
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TNF 可增强 CD57+ T 细胞通过血管内皮细胞的迁移:艾滋病病毒感染者心血管风险的新模型。
人类免疫缺陷病毒(PWH)感染者尽管通过抗逆转录病毒疗法实现了病毒抑制,但他们患动脉粥样硬化性心血管疾病的风险却比一般人更高,发病时间也更早。CD57+ T细胞很容易从动脉粥样硬化斑块中回收,并很可能通过靶向内皮细胞(ECs)而导致疾病,但促进这些细胞渗入斑块的具体机制仍然难以捉摸。在此,我们报告了一种新型检测方法的开发情况,该方法可量化 T 细胞对原发性人血管内皮细胞单层的粘附和通过单层的转运,结果表明 CD57+ T 细胞优先粘附于单层并通过单层转运。此外,用肿瘤坏死因子(TNF)激活血管内皮细胞可显著增加 CD57+ T 细胞的转运,从而支持 TNF 在促进 CD57+ T 细胞血管归巢中的作用。该模型将有助于阐明CD57+ T细胞渗入斑块的机制,并测试预防CD57+ T细胞渗入斑块的干预措施。
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来源期刊
CiteScore
3.10
自引率
6.70%
发文量
201
审稿时长
3-6 weeks
期刊介绍: AIDS Research and Human Retroviruses was the very first AIDS publication in the field over 30 years ago, and today it is still the critical resource advancing research in retroviruses, including AIDS. The Journal provides the broadest coverage from molecular biology to clinical studies and outcomes research, focusing on developments in prevention science, novel therapeutics, and immune-restorative approaches. Cutting-edge papers on the latest progress and research advances through clinical trials and examination of targeted antiretroviral agents lead to improvements in translational medicine for optimal treatment outcomes. AIDS Research and Human Retroviruses coverage includes: HIV cure research HIV prevention science - Vaccine research - Systemic and Topical PreP Molecular and cell biology of HIV and SIV Developments in HIV pathogenesis and comorbidities Molecular biology, immunology, and epidemiology of HTLV Pharmacology of HIV therapy Social and behavioral science Rapid publication of emerging sequence information.
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