Parallel studies of mucosal immunity in the reproductive and gastrointestinal mucosa of HIV-infected women.
Parallel studies of mucosal immunity in the reproductive and gastrointestinal mucosa of HIV-infected women.
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HIV感染妇女生殖和胃肠粘膜粘膜免疫的平行研究。
DOI：
10.1111/aji.13246
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Shacklett,BarbaraL
中科院分区：
文献类型：
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作者：
Shanmugasundaram,Uma;Critchfield,JWilliam;Giudice,LindaC;Smith-McCune,Karen;Greenblatt,RuthM;Shacklett,BarbaraL
HIV对胃肠道(GIT)的影响，包括CD4耗尽、上皮破坏和胶原沉积，已有很好的文献记载，但联合抗逆转录病毒治疗(CART)只能部分逆转。然而，艾滋病毒对女性生殖道(FRT)的影响知之甚少，大多数研究都集中在宫颈和阴道上，而没有评估上尿路。在这里，我们调查了HIV感染妇女子宫内膜和子宫内膜中的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进行比较。研究方法从18名妇女身上获取粘膜样本和血液：4名HIV阳性且在抽样前至少3年不在购物车上的妇女，包括2名自然控制者(病毒载量[VL]无法检测到和CD4>；350)；9名VL低到无法检测到VL的CART妇女；5名HIV未感染的妇女。粘膜样本包括回肠末端、乙状结肠、宫颈细胞刷、宫颈刮除和子宫内膜活检。结果CD38/HLA-DR共表达检测结果显示，CART后子宫内膜T细胞活性显著升高，而胃肠道组织中T细胞活性明显降低。在CART前后的回肠、结肠和子宫内膜组织中均检测到HIV特异性CD8+T细胞反应，且非CART组中HIV特异性CD8+T细胞反应的幅度更大。结论我们的研究结果揭示了胃肠道和生殖道中HIV+T细胞频率、免疫激活和HIV特异性T细胞反应的差异，并突出了HIV控制者和CART女性之间的差异。
ProblemThe 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.Method of StudyMucosal 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.ResultsT‐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.ConclusionOur 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.