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In Vitro Models of Human T Cell Development: Dishing Out Progenitor T Cells

机译:人类T细胞发育的体外模型:淘汰祖T细胞

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T cells develop within the unique microenvironment provided by the thymus. T cell differentiation involves a series of commitment events and developmental checkpoints including T cell receptor (TCR) gene recombination and positiveegative selection of developing thymocytes to yield functionally mature T cells. These events occur in a sequential, temporal and spatial fashion, as developing thymocytes migrate through the thymus. In vitro studies to yield insights into human T cell development have classically employed the fetal thymic organ culture (FTOC) model system. This approach relies on the seeding of human hematopoietic stem cells (HSCs) and/or their progeny into host thymic lobes or thymic fragments, typically of mouse origin. Recently, a novel in vitro approach that makes use of the OP9 bone marrow stromal cell line expressing the Notch receptor ligand Delta-like-1 (OP9-DL1) effectively supported the generation of large numbers of human progenitor T cells from HSCs. In this review, we outline several in vitro systems employed for the generation and study of human T cells. Particular emphasis is dedicated to the OP9-DL1 coculture system. Finally, given the number of progenitor T cells that can be generated in vitro, we discuss the potential implications for the treatment of immune-related diseases such as cancer, immunedeficiency, and autoimmunity.
机译:T细胞在胸腺提供的独特微环境中发育。 T细胞分化涉及一系列承诺事件和发展检查点,包括T细胞受体(TCR)基因重组和正/负选择发育中的胸腺细胞以产生功能成熟的T细胞。随着发育中的胸腺细胞迁移通过胸腺,这些事件以顺序,时间和空间的方式发生。为了获得对人类T细胞发育的见解的体外研究,经典地采用了胎儿胸腺器官培养(FTOC)模型系统。该方法依赖于将人类造血干细胞(HSC)和/或其后代接种到通常为小鼠来源的宿主胸腺叶或胸腺片段中。最近,一种新型的体外方法利用表达Notch受体配体Delta-like-1(OP9-DL1)的OP9骨髓基质细胞系,有效地支持了从造血干细胞产生大量人祖T细胞。在这篇综述中,我们概述了用于人类T细胞生成和研究的几种体外系统。特别强调OP9-DL1共培养系统。最后,鉴于可以在体外产生的祖T细胞数量,我们讨论了对免疫相关疾病(如癌症,免疫缺陷和自身免疫)的潜在治疗意义。

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