Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal (UQAM), Montreal, QC, Canada.
Research Institute of McGill University Health Centre, Montreal, QC, Canada.
Front Immunol. 2022 Jul 29;13:962912. doi: 10.3389/fimmu.2022.962912. eCollection 2022.
Besides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3 CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3 CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied.
Subsets of FoxP3 CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.5 months post-infection), ART-treated in chronic infection (n=10), elite controllers (n=18), and HIV-uninfected controls (n=21).
Acute and chronic infection were associated with increased total, effector memory, and terminally differentiated FoxP3 CD8 T-cells, while early ART normalized only the frequencies of total FoxP3 CD8 T-cells. We observed an increase in FoxP3 CD8 T-cell immune activation (HLADR/CD38), senescence (CD57/CD28), and PD-1 expression during acute and chronic infection, which were not normalized by early ART. FoxP3 CD8 T-cells in untreated participants expressed higher levels of immunosuppressive LAP(TGF-β1) and CD39 than uninfected controls, whereas early ART did not affect their expression. The expression of gut-homing markers CCR9 and Integrin-β7 by total FoxP3 CD8 T-cells and CD39 and LAP(TGF-β1) FoxP3 CD8 T-cells increased in untreated individuals and remained higher than in uninfected controls despite early ART. Elite controllers share most of the FoxP3 CD8 T-cell characteristics in uninfected individuals.
Although early ART normalized total FoxP3 CD8 T-cells frequencies, it did not affect the persistent elevation of the gut-homing potential of CD39 and LAP(TGF-β1) FoxP3 CD8 T-cell, which may contribute to immune dysfunction.
除了 CD4 调节性 T 细胞（Tregs）外，免疫抑制 FoxP3 CD8 T 细胞作为 Tregs 的一个重要亚群正在出现，这有助于 HIV 感染中的免疫功能障碍和疾病进展。然而，急性 HIV 感染和早期抗逆转录病毒治疗（ART）启动后 FoxP3 CD8 T 细胞的动态变化仍研究不足。
在未经治疗的急性（n=26）和慢性（n=10）HIV 感染个体、急性感染时早期接受 ART 治疗的个体（n=10，ART 开始中位时间：感染后 5.5 个月）、慢性感染时接受 ART 治疗的个体（n=10）、精英控制者（n=18）和 HIV 未感染者（n=21）的 PBMC 中，前瞻性和横断面描述 FoxP3 CD8 T 细胞亚群。
急性和慢性感染与总 FoxP3 CD8 T 细胞、效应记忆和终末分化 FoxP3 CD8 T 细胞的增加有关，而早期 ART 仅使总 FoxP3 CD8 T 细胞的频率正常化。我们观察到在急性和慢性感染期间 FoxP3 CD8 T 细胞的免疫激活（HLADR/CD38）、衰老（CD57/CD28）和 PD-1 表达增加，早期 ART 无法使其正常化。未经治疗的参与者的 FoxP3 CD8 T 细胞表达更高水平的免疫抑制 LAP（TGF-β1）和 CD39，而未感染者对照组则没有，而早期 ART 并没有影响其表达。总 FoxP3 CD8 T 细胞和 CD39 和 LAP（TGF-β1）FoxP3 CD8 T 细胞的肠道归巢标记物 CCR9 和整合素-β7 的表达在未经治疗的个体中增加，并且尽管接受了早期 ART，其表达仍高于未感染者对照组。精英控制者与未感染者个体的大多数 FoxP3 CD8 T 细胞特征相似。
尽管早期 ART 使总 FoxP3 CD8 T 细胞频率正常化，但它并未影响 CD39 和 LAP（TGF-β1）FoxP3 CD8 T 细胞持续升高的肠道归巢潜能，这可能有助于免疫功能障碍。
