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HIV-ART 对血液和女性生殖道黏膜中 Th17 和 Treg 细胞恢复的影响。

Impact of HIV-ART on the restoration of Th17 and Treg cells in blood and female genital mucosa.

机构信息

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.

Hospital J.A. Fernández, Buenos Aires, Argentina.

出版信息

Sci Rep. 2019 Feb 13;9(1):1978. doi: 10.1038/s41598-019-38547-1.

Abstract

The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level.

摘要

本研究旨在评估抗逆转录病毒治疗(ART)对 HIV 阴性、ART 初治和 ART 治疗的 HIV 阳性患者外周血和女性生殖道(FGT)中 Th17 和 Treg 细胞比例和功能的影响。为此,我们采集了 41 名 HIV 阴性、33 名 HIV 阳性且未接受 ART 治疗(ART-naive)和 32 名 HIV 阳性且接受 ART 治疗(ART+)的患者的样本。在外周血中,HIV+ART+患者中改变的 Th17 和 Th17/Treg 比例得到了正常化,但仍观察到某些异常的 Treg 和活化 T 细胞比例。在 FGT 中,与 HIV-neg 组相比,即使在 HIV+ART+女性的宫颈单核细胞(CMCs)中,也观察到与 Th17 相关细胞因子分泌异常的模式。此外,这些改变的分泌模式与 CXCL5 和 CXCL1 趋化因子水平降低以及 CC17/CC20 比值的免疫调节倾斜有关。最后,ART 并未恢复 PBMC 中具有肠道归巢潜力的 Th17 前体细胞的比例,并且这些细胞与 CMCs 产生的 IL-17F 和 IL-21 水平之间存在正相关,这可能表明这些细胞更好地归巢到肠道也意味着它们在女性生殖道中的更好恢复。这些结果表明,抗逆转录病毒治疗并未完全恢复女性黏膜水平的 Th17 相关免疫功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/008b/6374372/90c9c498dd1c/41598_2019_38547_Fig1_HTML.jpg

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