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在人类PCLS中调节T细胞组织的存在和激活

Tonia Bargmann^1,2,3, Charline Sommer^1,2,3, Lena Stowasser^1,2

¹Fraunhofer Institute for Toxicology and Experimental Medicine, Preclinical Pharmacology and Toxicology, Nikolai-Fuchs-Str. 1, Hannover, 30625, Germany.

Respiratory research

|November 15, 2025

概括

精密切割肺切片 (PCLS) 有效地模拟了肺免疫力,显示了T细胞对刺激的反应. 通过PCLS,可以分析本地肺微环境中的组织居住标记物和T细胞激活.

科学领域:

免疫学免疫学免疫学
呼吸系统医学呼吸系统医学
细胞生物学细胞生物学

背景情况:

居住性免疫细胞对于肺部特异性免疫是至关重要的.
精密切割的肺切片 (PCLS) 保持了原生肺微环境,用于ex vivo研究.
PCLS是分析居住记忆T细胞的居住和功能的一个很好的模型.

研究的目的:

通过PCLS研究本地肺部利基中的组织居住标记和T细胞激活的调节.
分析各种刺激对T细胞反应在肺微环境中的影响.

主要方法:

PCLS患者接受了转化生长因子-β (TGFβ),抗CD3/CD28,互白素-2 (IL-2) 和MHC-I受限制的治疗.
通过流细胞计和媒介分泌分析分析了反应.
评估了细胞因子分泌,CD4+/CD8+T细胞比率,以及激活/居住标记物的表达.

主要成果:

居民记忆T细胞在PCLS中很丰富.
组织居住标志物CD103的调节取决于TGFβ或IL-2信号与T细胞受体参与相结合.
T细胞激活上调了CD39,CD137和Ki-67等标记物,并增加了IFNγ,IL-2和Granzyme B等细胞因子的分泌,同时降低了TGFβ.
刺激MHC-I激活了T细胞和增加了炎症效应因子细胞因子的分泌.

结论:

PCLS作为一个有价值的ex vivo平台,用于研究人类肺组织微环境中的T细胞反应.
该模型允许调制和分析受局部因素影响的组织居民T细胞行为.

关键词:

活体外 (ex vivo) 生物体外.这是一种MHC-I.在PCLS中使用PCLS.聚克隆的t细胞激活召回响应召回响应居民记忆t细胞的存在.

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