Division of Hematology-Oncology, The David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2009 Dec 7;4(12):e8208. doi: 10.1371/journal.pone.0008208.
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.
目前非常需要有效的疗法来对抗慢性病毒感染。正常情况下，免疫反应能迅速控制大多数病毒感染，而旨在重新建立免疫控制的治疗策略可能是治疗持续性病毒感染的一种强有力方法。我们研究了通过基因编程使人类造血干细胞产生成熟的 CD8+细胞毒性 T 淋巴细胞，表达分子克隆的“转基因”人抗 HIV T 细胞受体（TCR）的潜力。将抗 HIV TCR 转导到人类造血干细胞中，指导了一大群多功能、针对 HIV 的 CD8+细胞的成熟，这些细胞能够识别和杀伤携带病毒抗原的细胞。因此，通过这个概念验证，我们提出通过基因工程改造人类造血干细胞将能够定制效应 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。
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