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Updated: Aug 12, 2025

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组织CD14⁺CD8⁺ T细胞被骨髓细胞重新编程并由LPS调节

Laura J Pallett¹, Leo Swadling², Mariana Diniz²

¹Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, UK. laura.pallett@ucl.ac.uk.

|January 25, 2023

概括

研究人员在肝脏中发现了一种独特的CD8+ T细胞子集,该细胞表达CD14. 这些CD14+CD8+T细胞具有免疫调节和增强的效应功能,对肝脏免疫至关重要.

科学领域:

免疫学
肝病学
细胞生物学

背景情况:

尽管肝脏经常接触细菌产品,如脂多糖 (LPS),但仍然保持免疫耐受性.
了解控制肝脏耐受性和免疫力的细胞机制对于治疗肝脏疾病和改善免疫疗法至关重要.
肝脏中耐受性和免疫性之间的切换在细胞水平上尚不完全理解.

研究的目的:

识别和描述人类肝脏中的新型CD8+T细胞子集.
研究这些独特的T细胞的功能性质和潜在来源.
研究这些细胞在肝脏移植,病毒感染,瘤和肝脏疾病中的作用.

主要方法:

流细胞测量用于识别和量化人肝样本中的CD14+CD8+T细胞,体,体和周围血液.
在T细胞受体 (TCR) 激活后评估细胞因子 (IL-10,IL-2) 和效应器功能 (抗病毒,抗瘤) 的活体功能测试.
在体外实验中研究T细胞获得髓膜蛋白以及LPS和CXCL12对T细胞表型和功能的影响.

主要成果:

在人类肝脏中发现了独特的CD14+CD8+T细胞群,通常在CD14高的骨髓细胞附近发现.
这些CD14+CD8+T细胞在肝脏异位移植,病毒反应,瘤透和肝硬化瘤中得到丰富.
CD14+CD8+T细胞表现出高活性,增加循环,构成性IL-10和IL-2的产生,以及增强的效应器功能.
包括LPS受体复合体在内的T细胞获得了CD14+CD8+T细胞表型和增强的抗瘤活性.
显示LPS和CXCL12对CD14+CD8+T细胞的频率和功能有影响,这表明细菌产物和结构相互作用的作用.

结论:

CD14+CD8+T细胞代表肝脏中具有显著的免疫调节和效应能力的独特的骨髓指导性T细胞子集.
这些细胞在肝脏微环境中参与肝脏异位移植的接受,抗病毒和抗瘤免疫力.
来自肠肝轴的细菌产物和局部结构因子可以通过骨髓指令调节CD8+T细胞功能来塑造肝脏免疫力.

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