在体外再刺激后,肠组织内存T细胞与循环内存T细胞保持着不同的身份
Ammarina Beumer-Chuwonpad1, Felix M Behr1, Floris P J van Alphen2
1Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, the Netherlands.
European journal of immunology
|March 19, 2024
概括
居民记忆T (TRM) 细胞对于早期感染防御至关重要. 这项研究表明,在低氧条件下培养TRM细胞允许它们扩张,同时保留其潜在免疫治疗的保护性记忆表型.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- T细胞研究的研究.
背景情况:
- 居民记忆T (TRM) 细胞提供了快速的保护,防止再感染,即使没有循环的记忆细胞.
- TRM细胞没有终端分化,可以在体内扩张,这表明免疫治疗中体外扩张的潜力.
- 在体内再刺激后,存在有关TRM细胞身份维护和潜在转化为循环记忆细胞的担忧.
研究的目的:
- 研究TRM细胞如何对培养中的抗原激活作出反应.
- 为了确定体外TRM扩张的最佳条件,同时保持其独特的表型和功能.
- 评估扩展TRM细胞在免疫疗法应用中的潜力.
主要方法:
- 使用了Listeria monocytogenes和LCMV感染的小鼠模型.
- 从小肠的上皮内区分隔离的TRM细胞.
- 在不同的条件下培养TRM细胞,包括低氧 (低氧).
- 分析了TRM表型,细胞因子生产,代谢概况和蛋白质组标记.
主要成果:
- 在抗原刺激和静止在同源性细胞因子中休息后,TRM细胞在体外扩大.
- 很大一部分扩展的TRM细胞保持了关键的TRM标志物 (CD69,CD103).
- 在培养过程中,低氧气压是保持TRM表型和相关分子的最佳选择.
- 扩展的TRM细胞保留了效应因子功能 (细胞因子生产),而没有采用效应因子T细胞代谢特征.
- 蛋白质组分析证实了TRM特定的转录因子,组织保留分子和代谢酶的保留.
结论:
- 低氧条件支持TRM细胞的体外扩张.
- 扩展的TRM细胞可以保持其特有的表型和效应器功能.
- 这些发现表明了治疗策略的前景,包括用于免疫治疗的体外TRM扩展.
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