Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.
Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.
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DOI：
10.1371/journal.pone.0008208
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发表时间：
2009-12-07
期刊：
影响因子：
3.7
通讯作者：
Zack JA
中科院分区：
文献类型：
--
作者：
Kitchen SG;Bennett M;Galić Z;Kim J;Xu Q;Young A;Lieberman A;Joseph A;Goldstein H;Ng H;Yang O;Zack JA
迫切需要有效的治疗方法来对抗慢性病毒感染。免疫应答通常在控制大多数病毒感染方面是挑剔的，并且旨在重建免疫控制的治疗策略代表了治疗持续性病毒感染的潜在有力方法。我们研究了基因编程人造血干细胞产生成熟的CD8+细胞毒性T淋巴细胞的潜力，这些细胞表达分子克隆的“转基因”人抗HIV T细胞受体（TCR）。人造血干细胞的抗HIV TCR转导指导了大量多功能HIV特异性CD8+细胞的成熟，这些细胞能够识别和杀死病毒抗原呈递细胞。因此，通过这种概念验证，我们提出，人类造血干细胞的基因工程将允许定制效应T细胞反应，以对抗HIV感染或其他以免疫控制丧失为特征的疾病。
There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, “transgenic” human anti-HIV T cell receptor (TCR). Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.
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