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在艾滋病毒感染者中,GNLY+CD8+ T 细胞是过早衰老和持续炎症的桥梁
Hui-Fang Wang1,2, Chao Zhang2, Li-Ping Zhang2
1Department of Infectious Diseases and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Emerging microbes & infections
|March 26, 2025
概括
艾滋病毒感染者因炎症而经历加速衰老. 格拉努利辛表达的CD8+ T细胞驱动这种情况,有助于炎症,但抗格拉努利辛抗体可以帮助减轻影响.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 老年学是一门学科.
背景情况:
- 艾滋病毒感染者 (PLWH) 呈现加速衰老和全身炎症.
- 在PLWH中,T细胞的克隆扩张是常见的,但其与炎症的联系尚未完全理解.
研究的目的:
- 调查T细胞受体 (TCR) 谱系在PLWH中炎症的作用.
- 确定驱动克隆扩张的特定T细胞群体及其对PLWH加速衰老的贡献.
主要方法:
- 在257个健康对照 (HC) 和228个PLWH中分析了TCRβ曲目.
- 单细胞RNA测序与TCR测序相结合.
- 用T细胞和单细胞进行体外实验,包括用互白素-15 (IL-15) 刺激和抗体治疗.
主要成果:
- PLWH表现出显著的T细胞克隆扩张,部分由抗逆转录病毒疗法 (ART) 逆转.
- 高细胞毒性和低耗尽性特征的花素阳性 (GNLY+) CD8+ T细胞是克隆扩张的主要驱动因素.
- IL-15激活GNLY+ CD8+ T细胞,促进炎症并破坏肠上皮细胞;抗GNLY抗体显示部分恢复.
结论:
- GNLY+ CD8+ T细胞是PLWH持续克隆扩张的核心驱动力.
- 这些细胞在炎症中发挥着至关重要的作用,这表明了缓解PLWH加速衰老的潜在治疗点.
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