Department of Biological Sciences, Université du Québec à Montréal (UQAM).
CHUM Research Centre.
AIDS. 2021 Jun 1;35(7):1003-1014. doi: 10.1097/QAD.0000000000002842.
Despite the success of antiretroviral therapy (ART) to control viral replication, people living with HIV (PWH) have high levels of chronic systemic inflammation and immune dysregulation which drives accelerated co-morbidities including coronary artery disease (CAD). Regulatory T cells (Tregs) and ectonucleotidases CD39/CD73 are known to be athero-protective via their immunosuppressive and anti-inflammatory functions.
We assessed the dynamics of Treg subsets in ART-treated PWH with or without CAD vs. HIV-uninfected individuals.
Blood specimens were obtained from 142 participants including ART-treated HIV-infected adults with (n = 43) or without CAD (n = 41), as well as HIV-uninfected controls with (n = 31) or without CAD (n = 27). CAD was determined by the presence of atherosclerotic features on computed tomography angiography of the coronary arteries performed on all study participants. Treg subsets frequencies were assessed by flow cytometry.
Regardless of statin treatment or ART regimen, HIV+CAD+ individuals had the highest total Treg frequencies and increased thymic generation and output of Tregs (Helios/CD31 expression), while athero-protective CD39+/CD73+ Tregs were significantly depleted in this group. Tregs from PWH had higher expression of CCR6/CXCR3 than uninfected individuals regardless of CAD, while in HIV+CAD+ individuals Tregs expressed the highest levels of CCR4, which limits their maintenance. The lowest levels of CD4+ and CD8+ T-cell immune activation has been observed in HIV+CAD+ within study groups.
ART-treated PWH with diagnosed CAD are characterized by profound alterations in populations of anti-inflammatory and athero-protective Treg subsets. These changes may contribute to atherosclerotic plaque formation and progression during chronic HIV infection in the ART era.
尽管抗逆转录病毒疗法（ART）成功控制了病毒复制，但艾滋病毒感染者（PWH）仍存在高水平的慢性系统性炎症和免疫失调，这会加速合并症的发生，包括冠心病（CAD）。调节性 T 细胞（Tregs）和外核苷酸酶 CD39/CD73 因其免疫抑制和抗炎功能而具有抗动脉粥样硬化作用。
我们评估了接受 ART 治疗的 PWH 中 Treg 亚群的动态变化，包括有或无 CAD 的 PWH 与未感染 HIV 的个体进行比较。
从 142 名参与者中采集了血液样本，包括接受 ART 治疗的 HIV 感染成人，其中有 CAD（n = 43）或无 CAD（n = 41），以及未感染 HIV 的对照者，其中有 CAD（n = 31）或无 CAD（n = 27）。通过对所有研究参与者的冠状动脉计算机断层血管造影术确定 CAD 的存在。通过流式细胞术评估 Treg 亚群的频率。
无论他汀类药物治疗或 ART 方案如何，HIV+CAD+个体的总 Treg 频率最高，并且胸腺产生和 Treg 的输出增加（Helios/CD31 表达），而该组中保护性 CD39+/CD73+ Treg 明显减少。无论是否存在 CAD，来自 PWH 的 Tregs 比未感染的个体表达更高的 CCR6/CXCR3，而在 HIV+CAD+个体中，Tregs 表达最高水平的 CCR4，这限制了它们的维持。在研究组中，HIV+CAD+个体的 CD4+和 CD8+ T 细胞免疫激活水平最低。
已诊断 CAD 的接受 ART 治疗的 PWH 表现为抗炎和抗动脉粥样硬化 Treg 亚群的显著改变。这些变化可能导致在 ART 时代慢性 HIV 感染期间动脉粥样斑块的形成和进展。
