抑制NADase CD38可以改善细胞巨乳病毒特异性的CD8+ T细胞功能和代谢
Nils Mülling1,2, Felix M Behr1, Graham A Heieis3
1Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
The Journal of clinical investigation
|July 2, 2024
概括
细胞巨乳病毒 (CMV) 感染会影响移植受体的CD8+T细胞代谢. 抑制CD38恢复了这些免疫细胞的活力,提高了它们对抗病毒的能力.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 代谢过程中的代谢.
背景情况:
- 细胞巨乳病毒 (CMV) 是免疫功能低下个体,特别是移植接受者 (KTRs) 的一个重要的机会性病原体.
- 在免疫抑制患者中,限制T细胞对CMV有效性的确切机制尚不清楚.
研究的目的:
- 为了研究KTRs中非控制的CMV感染的CMV特异性CD8+T细胞的代谢状态.
- 确定恢复抗CMV免疫反应的治疗点.
主要方法:
- 来自KTRs的CMV特异性CD8+T细胞的深入代谢概况.
- 对T细胞的转录,蛋白质和功能水平的分析.
- 在试验室和CMV感染的小鼠模型中抑制CD38活性.
主要成果:
- 在KTR中,CMV特异性的CD8+ T细胞表现出代谢失调,包括糖分分解受损和线粒体应激增加.
- 观察到尼古丁胺胺氨基丁核酸核酶 (NADase) CD38的表达升高.
- 抑制CD38恢复了T细胞代谢,并增强了细胞因子的产生.
- 这些发现在免疫抑制的CMV感染小鼠模型中得到了验证.
结论:
- CD8+ T 细胞的代谢功能障碍有助于KTRs中不受控制的CMV感染.
- 向CD38提供了一种潜在的策略,可以逆转T细胞低响应性,并改善免疫受损个体的病毒控制.
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