Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory National Primate Research Center (ENPRC), Emory University, Atlanta, GA, United States.
Division of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, United States.
Front Immunol. 2024 Sep 25;15:1456652. doi: 10.3389/fimmu.2024.1456652. eCollection 2024.
Ovarian hormones are known to modulate the immune system in the female genital tract (FGT). We sought to define the impact of the menstrual cycle on the mucosal HIV target cell levels, and tissue-resident CD4 T cells.
Here, we characterized the distribution, phenotype, and function of CD4 T cells with special emphasis on HIV target cells (CCR5+ and α4β7+) as well as tissue-resident memory (TRM; CD69+ and CD103+) CD4 T cells in FGT of cycling women. Peripheral blood and Endocervical cells (EC-collected from cytobrush) were collected from 105 healthy women and performed multicolor flow cytometry to characterize the various subsets of CD4 T cells. Cervicovaginal lavage (CVL) were collected for cytokine analysis and plasma were collected for hormonal analysis. All parameters were compared between follicular and luteal phase of menstrual cycle.
Our findings revealed no significant difference in the blood CD4 T cell subsets between the follicular and luteal phase. However, in EC, the proportion of several cell types was higher in the follicular phase compared to the luteal phase of menstrual cycle, including CCR5+α4β7-cells (p=0.01), CD69+CD103+ TRM (p=0.02), CCR5+CD69+CD103+ TRM (p=0.001) and FoxP3+ CD4 T cells (p=0.0005). In contrast, α4β7+ CCR5- cells were higher in the luteal phase (p=0.0004) compared to the follicular phase. In addition, we also found that hormonal levels (P4/E2 ratio) and cytokines (IL-5 and IL-6) were correlated with CCR5+ CD4 T cells subsets during the follicular phase of the menstrual cycle.
Overall, these findings suggest the difference in the expression of CCR5 and α4β7 in TRM CD4 T cell subsets in endocervix of HIV seronegative women between the follicular and luteal phase. Increase in the CCR5+ expression on TRM subsets could increase susceptibility to HIV infection during follicular phase of the menstrual cycle.
已知卵巢激素可调节女性生殖道（FGT）中的免疫系统。我们旨在确定月经周期对黏膜 HIV 靶细胞水平和组织驻留 CD4 T 细胞的影响。
在这里，我们描述了 CD4 T 细胞的分布、表型和功能，特别强调了 HIV 靶细胞（CCR5+和 α4β7+）以及组织驻留记忆（TRM；CD69+和 CD103+）CD4 T 细胞在循环女性的 FGT 中的分布。从 105 名健康女性中采集外周血和宫颈内细胞（EC-用 cytobrush 收集），并进行多色流式细胞术以表征 CD4 T 细胞的各种亚群。采集宫颈阴道灌洗（CVL）进行细胞因子分析，并采集血浆进行激素分析。将所有参数在卵泡期和黄体期之间进行比较。
我们的研究结果显示，血液 CD4 T 细胞亚群在卵泡期和黄体期之间没有明显差异。然而，在 EC 中，与黄体期相比，几种细胞类型在卵泡期的比例更高，包括 CCR5+α4β7-细胞（p=0.01）、CD69+CD103+ TRM（p=0.02）、CCR5+CD69+CD103+ TRM（p=0.001）和 FoxP3+ CD4 T 细胞（p=0.0005）。相比之下，α4β7+CCR5-细胞在黄体期（p=0.0004）更高。此外，我们还发现激素水平（P4/E2 比值）和细胞因子（IL-5 和 IL-6）与月经周期卵泡期的 CCR5+CD4 T 细胞亚群相关。
总的来说，这些发现表明在 HIV 血清阴性女性的宫颈内，CCR5 和 α4β7 在 TRM CD4 T 细胞亚群中的表达在卵泡期和黄体期之间存在差异。TRM 亚群中 CCR5 表达的增加可能会增加月经周期卵泡期感染 HIV 的易感性。
