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稳定状态,治疗和虫诱导的IL-4妥协保护性CD8 T细胞旁观者激活

Nicholas J Maurice^1,2, Talia S Dalzell^1,2, Nicholas N Jarjour^1,2

¹Center for Immunology, University of Minnesota Medical School, Minneapolis, MN.

bioRxiv : the preprint server for biology

|June 25, 2024

概括

洲际蛋白-4 (IL-4) 对抗IL-18传感,损害了记忆CD8T细胞 (Tmem) 的旁观者激活. 抗原经验取代了这些缺陷,增强了Tmemmem.

科学领域:

免疫学免疫学免疫学
细胞免疫学细胞免疫学
这是天生的免疫力.

背景情况:

记忆CD8T细胞 (Tmem) 在IL-12,IL-15和IL-18等细胞因子激活后表现出与生俱来的类似杀手功能.
旁观者激活的现象,Tmem的激活独立于直接的抗原识别,对于适应性免疫至关重要,但其调节机制仍然不完全理解.

研究的目的:

研究调节旁观者激活记忆CD8T细胞的机制.
阐明IL-4/IL-18轴在调节旁观者激活中的作用.
为了确定抗原体验如何影响旁观者激活能力.

主要方法:

使用特定无病原体的小鼠模型来评估旁观者激活的菌株内在差异.
使用细胞因子刺激 (IL-4,IL-18) 和虫感染模型.
分析细胞毒性媒介体 (granzymes,干扰素-γ) 和IL-18受体的表达.

主要成果:

观察到旁观者激活的压力内在缺陷,归因于基底IL-4信号,对抗IL-18传感.
发现治疗性和虫诱导的IL-4会损害旁观者介导的保护性反应.
IL-4/IL-18轴微调细胞毒性媒介表达,而不是完全取消旁观者激活.
经过抗原测试的Tmem表现出均的IL-18受体表达和增强的旁观者激活能力,超过了菌株特定的缺陷.

结论:

旁观者激活是一个微调的过程,不是二进制的,可以通过共感染期间升高的细胞因子来调节.
抗原经验记忆CD8 T细胞对于强大的旁观者激活和细胞毒性反应至关重要.
了解IL-4/IL-18轴和抗原经验的作用对于剖析Tmem对健康和疾病的贡献至关重要.

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