诱导多能干细胞
重编程
抗原
生物
细胞毒性T细胞
T细胞
细胞疗法
免疫疗法
CD8型
细胞生物学
干细胞
祖细胞
造血
免疫学
癌症研究
细胞
免疫系统
体外
胚胎干细胞
遗传学
基因
作者
Toshinobu Nishimura,Hiromitsu Nakauchi
出处
期刊:Methods in molecular biology
日期:2019-01-01
卷期号:: 25-40
被引量:14
标识
DOI:10.1007/978-1-4939-8938-6_3
摘要
Human induced pluripotent stem cells (iPSCs) are a potential source of blood cells for transfusion therapies and a promising tool for studying the ontogeny of hematopoiesis. The development of widely varying reprogramming methods has enabled us nowadays to obtain iPSCs even from a small number of antigen-specific T cells from patients. As these T-cell-derived iPSCs (T-iPSCs) carry TCR gene rearrangements in their genomic DNA, they are likely useful for producing antigen-specific T cells and for studying T-cell development. T-cell immunotherapy is potentially an effective therapeutic strategy against many types of cancers and viral infections. If antigen-specific T cells tailored against diseases and for patients can be easily obtained, T-cell immunotherapy should become a popular choice of therapy. Here, we show the in vitro way to guide T-iPSCs sequentially to yield hematopoietic stem/progenitor cells (HSPCs), T-lineage cells, and mature CD8 single-positive T cells. These in vitro-generated CD8+ T cells display antigen-specific cytotoxity and perform general T-cell functions. This novel protocol thus provides means to generate antigen-specific T cells as well as chances to study normal human lymphopoiesis. It may help identify, and then clear away, barriers to T-cell immunotherapy such as immunological tolerance and cell exhaustion. T-iPSCs can confer their juvenile status upon their descendant T cells during pluripotency reprogramming and redifferentiation. This phenomenon should help to eliminate T-cell exhaustion.
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