Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.
Am J Reprod Immunol. 2020 Jul;84(1):e13246. doi: 10.1111/aji.13246. Epub 2020 May 8.
The effects of HIV on the gastrointestinal tract (GIT), including CD4 depletion, epithelial disruption, and collagen deposition, are well documented and only partially reversed by combination antiretroviral therapy (cART). However, the effects of HIV on the female reproductive tract (FRT) are poorly understood, and most studies have focused on ectocervix and vagina without assessing the upper tract. Here, we investigated CD4 T-cell frequency, phenotype, and HIV-specific T-cell responses in the endocervix and endometrium of HIV-infected women, comparing these tissues to the GIT.
Mucosal samples and blood were obtained from 18 women: four who were HIV-positive and not on cART for at least 3 years prior to sampling, including two natural controllers (viral load [VL] undetectable and CD4 >350); nine women on cART with low to undetectable VL; and five HIV-uninfected women. Mucosal samples included terminal ileum, sigmoid colon, endocervical cytobrush, endocervical curettage, and endometrial biopsy. T-cell frequency, phenotypes, and HIV-specific T-cell responses were analyzed by multiparameter flow cytometry.
T-cell activation, measured by CD38/HLA-DR co-expression, remained significantly elevated in endometrium following cART, but was lower in gastrointestinal tissues. HIV-specific CD8 T-cell responses were detected in ileum, colon, and endometrial tissues of women both on and off cART, and were of higher magnitude on those not on cART.
Our findings reveal differences in CD4 T-cell frequencies, immune activation, and HIV-specific T-cell responses between the gastrointestinal and reproductive tracts, and highlight differences between HIV controllers and women on cART.
艾滋病毒对胃肠道（GIT）的影响，包括 CD4 细胞耗竭、上皮细胞破坏和胶原蛋白沉积，已有充分记录，但仅部分通过联合抗逆转录病毒疗法（cART）得到逆转。然而，艾滋病毒对女性生殖道（FRT）的影响了解甚少，大多数研究集中在外阴和阴道，而没有评估上生殖道。在这里，我们调查了感染艾滋病毒的女性的宫颈内和子宫内膜中的 CD4 T 细胞频率、表型和 HIV 特异性 T 细胞反应，并将这些组织与 GIT 进行了比较。
从 18 名妇女中获得了粘膜样本和血液：四名妇女 HIV 阳性，在采样前至少 3 年未接受 cART，包括两名自然控制器（病毒载量[VL]不可检测和 CD4 > 350）；九名接受 cART 的妇女，VL 低至不可检测；和五名 HIV 未感染的妇女。粘膜样本包括末端回肠、乙状结肠、宫颈刷、宫颈刮除术和子宫内膜活检。通过多参数流式细胞术分析 T 细胞频率、表型和 HIV 特异性 T 细胞反应。
在接受 cART 后，子宫内膜中 T 细胞激活，以 CD38/HLA-DR 共表达测量，仍显著升高，但在胃肠道组织中较低。在接受和未接受 cART 的妇女的回肠、结肠和子宫内膜组织中均检测到 HIV 特异性 CD8 T 细胞反应，并且在未接受 cART 的妇女中反应幅度更高。
我们的研究结果揭示了胃肠道和生殖道之间 CD4 T 细胞频率、免疫激活和 HIV 特异性 T 细胞反应的差异，并强调了 HIV 控制器和接受 cART 的妇女之间的差异。
