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人胸腺移植免疫缺陷小鼠中人胸腺细胞的长期存活与分化

Long-term survival and differentiation of human thymocytes in human thymus-grafted immunodeficient mice.

作者信息

Tang Yang, Yang Yong-Guang, Bai Ou, Xia Jinxing, Hu Zheng

机构信息

Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, 130061, PR China.

Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.

出版信息

Immunotherapy. 2019 Jul;11(10):881-888. doi: 10.2217/imt-2019-0030. Epub 2019 May 29.

Abstract

Thymus transplants have produced encouraging clinical outcomes in achieving thymopoiesis and T-cell development. This study was aimed to investigate whether human thymus contains self-renewing lymphoid progenitors capable of maintaining long-term T-cell development. Immunodeficient mice were transplanted with human thymic tissue along with autologous GFP-expressing or allogeneic CD34 cells and followed for human thymopoiesis and T-cell development from the thymic progenitors versus CD34 cells, which can be distinguished by GFP or HLA expression. In both models, long-term thymopoiesis and T-cell development from the thymic grafts were detected. In these mice, human thymic progenitor-derived T cells including CD45RACD31CD4 new thymic emigrants were persistently present in the periphery throughout the observation period (32 weeks). The results indicate that human thymus contains long-lived lymphoid progenitors that can maintain durable thymopoiesis and T-cell development.

摘要

胸腺移植在实现胸腺生成和T细胞发育方面已产生了令人鼓舞的临床结果。本研究旨在调查人类胸腺是否含有能够维持长期T细胞发育的自我更新淋巴细胞祖细胞。将人类胸腺组织与自体表达绿色荧光蛋白(GFP)的细胞或同种异体CD34细胞一起移植到免疫缺陷小鼠体内,并追踪胸腺祖细胞与CD34细胞(可通过GFP或人类白细胞抗原(HLA)表达加以区分)来源的人类胸腺生成和T细胞发育情况。在两种模型中,均检测到了来自胸腺移植物的长期胸腺生成和T细胞发育。在这些小鼠中,在整个观察期(32周)内,外周持续存在源自人类胸腺祖细胞的T细胞,包括CD45RA⁺CD31⁻CD4⁺新胸腺迁出细胞。结果表明,人类胸腺含有可维持持久胸腺生成和T细胞发育的长寿淋巴细胞祖细胞。

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