来自PWH的血管性CD8T细胞诱导了依赖Granzymes的PAR1激活,促进了内皮炎症
Tong Li1, Chinmayee Mehta1, Cooper James1
1Department of Microbiology and Immunology, Georgetown University School of Medicine. Washington DC, USA.
bioRxiv : the preprint server for biology
|October 1, 2025
概括
在艾滋病毒感染者中,改变的CD8 T细胞损害了血管修复,增加了心血管疾病的风险. 了解这些免疫变化对于管理与艾滋病毒有关的心血管并发症至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管科学 心血管科学
- 病毒学 病毒学
背景情况:
- 艾滋病毒感染者 (PWH) 因T细胞免疫激活和内皮炎症而面临心血管风险升高.
- 关联艾滋病毒,免疫激活和心血管疾病的确切机制尚不清楚.
- 蛋白酶激活受体1 (PAR1) 参与凝血,内皮细胞和炎症部位的CD8 T细胞.
研究的目的:
- 研究HIV驱动的CD8 T细胞免疫激活如何影响内皮细胞修复机制.
- 确定参与内皮细胞修复的特定CD8T细胞子集及其在PWH中的功能.
主要方法:
- 在LCMV感染期间识别具有记忆前体表型的CD31高CD8T细胞.
- 在PWH中分析CD8 Tang (血管性T) 细胞频率,表型和大酶表达.
- 在体外研究评估了在人类内皮细胞中依赖于酶的PAR1激活.
主要成果:
- 一个CD8T细胞的子集与记忆前体表型和VEGF分泌被确定后病毒控制.
- 在PWH中,CD8 Tang细胞的频率降低,表型活化,酶表达增加.
- GZMA+GZMB+CD8 Tang细胞与动脉样硬化心血管疾病 (ASCVD) 风险相关.
- 在体外,酶激活PAR1,从内皮细胞中诱导促炎性细胞因子的释放.
结论:
- CD8 T细胞在病毒免疫和内皮恒温中发挥作用.
- 艾滋病毒诱导的免疫激活会破坏CD8T细胞功能,可能会损害内皮细胞的修复,并导致心血管风险.
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