Preserved Mucosal-Associated Invariant T Cells in the Cervical Mucosa of HIV-Infected Women with Dominant Expression of the TRAV1-2–TRAJ20 T Cell Receptor α-Chain

Anna Gibbs, K. Healy, Vilde Kaldhusdal, C. Sundling, Mathias Franzén-Boger, Gabriella Edfeldt, M. Buggert, J. Lajoie, K. Fowke, J. Kimani, D. Kwon, S. Andersson, J. Sandberg, K. Broliden, Haleh Davanian, M. Chen, Annelie Tjernlund
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引用次数: 1

Abstract

Abstract Background Mucosa-associated invariant T (MAIT) cells are innate-like T cells with specialized antimicrobial functions. Circulating MAIT cells are depleted in chronic human immunodeficiency virus (HIV) infection, but studies examining this effect in peripheral tissues, such as the female genital tract, are lacking. Methods Flow cytometry was used to investigate circulating MAIT cells in a cohort of HIV-seropositive (HIV+) and HIV-seronegative (HIV−) female sex workers (FSWs), and HIV− lower-risk women (LRW). In situ staining and quantitative polymerase chain reaction were performed to explore the phenotype of MAIT cells residing in paired cervicovaginal tissue. The cervicovaginal microbiome was assessed by means of 16S ribosomal RNA gene sequencing. Results MAIT cells in the HIV+ FSW group were low in frequency in the circulation but preserved in the ectocervix. MAIT cell T-cell receptor gene segment usage differed between the HIV+ and HIV− FSW groups. The TRAV1-2–TRAJ20 transcript was the most highly expressed MAIT TRAJ gene detected in the ectocervix in the HIV+ FSW group. MAIT TRAVJ usage was not associated with specific genera in the vaginal microbiome. Conclusions MAIT cells residing in the ectocervix are numerically preserved irrespective of HIV infection status and displayed dominant expression of TRAV1-2–TRAJ20. These findings have implications for understanding the role of cervical MAIT cells in health and disease.
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TRAV1-2-TRAJ20 T细胞受体α-链显性表达的hiv感染妇女宫颈黏膜中保存的粘膜相关不变性T细胞
黏膜相关不变性T细胞(Mucosa-associated invariant T, MAIT)是具有特殊抗菌功能的先天样T细胞。在慢性人类免疫缺陷病毒(HIV)感染中,循环MAIT细胞被耗尽,但在外周组织(如女性生殖道)中检测这种影响的研究缺乏。方法采用流式细胞术检测HIV-血清阳性(HIV+)和HIV-血清阴性(HIV -)女性性工作者(FSWs)和HIV-低危女性(LRW)的循环MAIT细胞。采用原位染色和定量聚合酶链反应研究MAIT细胞在配对宫颈阴道组织中的表型。采用16S核糖体RNA基因测序方法评估宫颈阴道微生物组。结果HIV+ FSW组MAIT细胞在循环中频率较低,但保留在子宫颈外。MAIT细胞t细胞受体基因片段的使用在HIV+和HIV - FSW组之间存在差异。TRAV1-2-TRAJ20转录本是HIV+ FSW组子宫颈外检测到的最高表达的MAIT TRAJ基因。MAIT TRAVJ的使用与阴道微生物组中的特定属无关。结论不论HIV感染情况如何,宫颈外存活的MAIT细胞均有一定数量的保存,且TRAV1-2-TRAJ20的表达占主导地位。这些发现有助于理解宫颈MAIT细胞在健康和疾病中的作用。
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