在持续的HBV感染中,IL-15通过新陈代谢再平衡来增强激活的HBV核心特异性CD8+原始细胞
Julia Peña-Asensio1,2, Henar Calvo-Sánchez3,4,2, Joaquín Miquel3,2
1Department of Biology of Systems, University of Alcalá, 28801 Alcalá de Henares, Madrid, Spain.
iScience
|December 29, 2023
概括
恢复HBV特异性CD8+原始细胞中的能量平衡可以在慢性乙型肝炎中恢复它们的功能.IL-15疗法在增强T细胞激活和效应器功能方面显示出有前途,以改善结果.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 慢性乙型肝炎 (CHB) 的特征是HBV特异性CD8+T细胞反应受损.
- 阴性E抗原 (CHBe(-)) CHB患者通常具有功能障碍的HBV核心特异性CD8+T细胞.
- 了解T细胞原始子集及其代谢调节对于治疗开发至关重要.
研究的目的:
- 研究IL-15和IL-2在调节HBV特异性CD8+T细胞原生子集的代谢状态和功能的作用.
- 探索IL-15/anti-PD-L1疗法的潜力,以恢复CHBe(-) 患者的T细胞活性.
主要方法:
- 静止前体 (QP) 和激活前体 (AP) 的流细胞计分析 HBV 核心特定的 CD8+ T 细胞子集.
- 评估T细胞激活标记物,代谢概况 (mTORC1) 和效应器功能.
- 在临床预测模型中评估IL-15/anti-PD-L1的治疗疗效.
主要成果:
- 特定于HBVcore的CD8+ QP细胞表现出类似记忆的表型,并在与抗原相遇时分化为AP细胞.
- 与IL-2相比,IL-15促进了具有触媒特征的持续T细胞激活,增强了增殖后代 (PP) 效应器功能.
- 接受NUC治疗的CHBe(-) 患者表现出与功能失调的PP细胞相关的合成AP表型.
- IL-15/anti-PD-L1治疗恢复了CHBe的反应性(-) 患者,自发恢复的可能性很低.
结论:
- 在AP细胞中重新平衡能量代谢是恢复CHBe中的PP功能的关键.
- IL-15通过调节能量新陈代谢来增强T细胞的反应,促进 catabolic 状态以改善效应器功能.
- IL-15/anti-PD-L1免疫疗法提供了一种潜在的策略,以重振CHB中耗尽的HBV特异性CD8+T细胞.
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