暂时抑制I型干扰素可以增强CD8+T细胞干细胞和疫苗保护
bioRxiv : the preprint server for biology
|July 9, 2024
概括
在病毒感染期间暂时阻止I型干扰素受体 (IFNAR) 促进干细胞样记忆T (T_SCM) 细胞的发展. 这一策略增强了疫苗诱导的对慢性感染的保护.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 病毒学 病毒学
背景情况:
- 开发诱导强大的CD8+T细胞记忆的疫苗,特别是干细胞样记忆T (T_SCM) 细胞,对于传染病控制和癌症免疫治疗至关重要.
- 对于产生长寿T_SCM细胞的精确发育要求仍然不完全理解.
研究的目的:
- 确定I型干扰素受体 (IFNAR) 阻断的最佳时间,以促进T_SCM细胞的产生.
- 阐明IFNAR封锁影响T_SCM分化和功能的机制.
主要方法:
- 在急性病毒感染期间调查了IFNAR阻塞的时间窗口.
- 利用转录概况来区分T_SCM细胞及其前体 (T_PEX).
- 评估了T细胞在淋巴结中的定位,并将其与化学激素表达相关联.
- 在挑战模型中,结合IFNAR抑制与mRNA-LNP疫苗接种.
主要成果:
- 确定了IFNAR阻断驱动T_SCM细胞形成的早期,短暂的窗口.
- 在病毒清除过程中,T_SCM细胞从过渡性耗尽 (T_PEX) 状态的前体中出现.
- IFNAR阻塞增加了IFNψ的产生,改变了CXCR3连接体的丰富性,并促进了T细胞在淋巴结对皮层中的保留.
- 结合IFNAR抑制和mRNA-LNP疫苗接种增强了T_SCM分化和对慢性感染的保护.
结论:
- 在病毒感染期间早期,暂时的IFNAR抑制促进T_SCM细胞分化而不会导致慢性感染.
- T_SCM和T_PEX状态在转录和表型上是不同的,在病毒清除过程中T_PEX产生的T_SCM.
- 暂时的IFNAR阻塞利用IFNψ调节CXCR3介导的T细胞局部化,将T_SCM分化与淋巴结保留相结合.
- 通过mRNA-LNP疫苗接种针对T_SCM细胞的有针对性的促进提供了一个有希望的战略,以加强对慢性病毒挑战的保护.
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