Nuffield Department of Women's & Reproductive Health, University of Oxford, The Women's Centre, John Radcliffe Hospital, Oxford, UK.
South African Medical Research Council Developmental Pathways for Health Research Unit, Department of Paediatrics, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Am J Reprod Immunol. 2020 Jun;83(6):e13240. doi: 10.1111/aji.13240. Epub 2020 Apr 12.
Human immunodeficiency virus (HIV) infection is associated with an increased risk of adverse pregnancy outcomes, including preterm birth (PTB), despite viral suppression with antiretroviral therapy. Mucosal-associated invariant T (MAIT) cells are an immune cell subset involved in antimicrobial immunity at mucosal surfaces. MAIT cells have been found at the maternal-foetal interface, and MAIT cells are typically depleted early in HIV infection. We aimed to investigate changes in MAIT cells in relation to maternal HIV/ART status and PTB.
We conducted flow cytometric analysis of peripheral blood samples from 47 HIV-positive (HIV+) and 45 HIV-negative (HIV-) pregnant women enrolled in a prospective pregnancy cohort study in Soweto, South Africa. Frequencies of Vα7.2+ CD161++ MAIT cells and proportions of CD4 , CD8 and double-negative MAIT cells were compared between women with and without HIV infection, and between women with and without PTB or spontaneous preterm labour (Sp-PTL).
Although overall MAIT cell frequencies were the same between HIV+ and HIV- patients, HIV+ patients had a higher proportion of CD8 MAIT cells in the first two trimesters. Women with PTB and Sp-PTL also had a higher proportion of CD8 MAIT cells in the first trimester compared to women without these outcomes. The association between changes in MAIT cell subsets and PTB/Sp-PTL was present in both HIV+ and HIV- women, and an additive effect on MAIT cell subsets was seen in women with both HIV infection and PTB.
Interactions between HIV-related and pregnancy-related changes in MAIT cell subsets and distribution may lead to imbalances in peripheral MAIT cell subsets in early pregnancy. This may contribute to the increased risk of PTB in HIV+ patients by altering the overall functionality of the peripheral MAIT cell compartment.
尽管抗逆转录病毒疗法(ART)可抑制病毒,但人类免疫缺陷病毒(HIV)感染与不良妊娠结局风险增加相关,包括早产(PTB)。黏膜相关不变 T(MAIT)细胞是参与黏膜表面抗菌免疫的免疫细胞亚群。在母体-胎儿界面发现了 MAIT 细胞,并且在 HIV 感染早期 MAIT 细胞通常会被耗尽。我们旨在研究 MAIT 细胞的变化与母体 HIV/ART 状态和 PTB 的关系。
我们对来自南非索韦托前瞻性妊娠队列研究中的 47 名 HIV 阳性(HIV+)和 45 名 HIV 阴性(HIV-)孕妇的外周血样本进行了流式细胞术分析。比较了 HIV 感染妇女与非 HIV 感染妇女、PTB 或自发性早产(Sp-PTL)妇女与非这些结局妇女之间,MAIT 细胞的 Vα7.2+ CD161++频率和 CD4、CD8 和双阴性 MAIT 细胞的比例。
尽管 HIV+和 HIV-患者的 MAIT 细胞频率总体相同,但 HIV+患者在前两个三个月中 CD8 MAIT 细胞比例更高。与没有这些结局的妇女相比,PTB 和 Sp-PTL 的妇女在第一个三个月中也有更高比例的 CD8 MAIT 细胞。在 HIV+和 HIV-妇女中,MAIT 细胞亚群的变化与 PTB/Sp-PTL 之间的关联存在,并且在同时患有 HIV 感染和 PTB 的妇女中,MAIT 细胞亚群的累加效应可见。
MAIT 细胞亚群和分布与 HIV 相关和妊娠相关变化之间的相互作用可能导致早孕外周 MAIT 细胞亚群失衡。这可能通过改变外周 MAIT 细胞区室的整体功能,增加 HIV 阳性患者 PTB 的风险。