Redifferentiation of Adaptive Na?ve-Like CTL from T-Cell-Derived iPSC
Redifferentiation of Adaptive Na?ve-Like CTL from T-Cell-Derived iPSC
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从 T 细胞衍生的 iPSC 中再分化适应性幼稚样 CTL
DOI：
10.1007/978-1-4939-9728-2_7
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Kaneko Shin
中科院分区：
文献类型：
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作者：
Kawai Yohei;Kaneko Shin
在本章中，我们描述了在10个T1/2和OP9/DL1饲养层条件下，从IPSCs到CD8CD8αβ+细胞毒T细胞的再分化过程。这里使用的IPSC是由T细胞克隆(T-IPSC)衍生而来的，T-IPSC在克隆过程中失去了幼稚表型，获得了疲惫/衰老表型(注1)。另一方面，重新分化的T细胞(T-IPSC-ts)重新获得原始表型(CD45RA+CD45RO−CCR7+CD62L+)，据报道，这些表型对输注的T细胞在体内的持久性至关重要，并极大地影响过继免疫治疗的疗效。事实上，与亲本T细胞克隆相比，T-IPSC-ts表现出更好的增殖能力，同时保持了同等的效应功能。在这里，我们展示了生产幼稚类T-IPSC-ts的方法，这可能是过继免疫治疗的有效细胞来源。
In this chapter, we describe redifferentiation procedures from iPSCs to CD8αβ+cytotoxic T cells in 10 T1/2 and OP9/DL1 feeder condition. iPSC used here is derived from T-cell clone (T-iPSC), which has lost naïve phenotype and acquired exhaustion/senescence phenotype during cloning process (Note 1). On the other hand, redifferentiated T cells (T-iPSC-Ts) reacquire naïve phenotype (CD45RA+CD45RO−CCR7+CD62L+), which are reportedly critical for in vivo persistence of infused T cells and greatly affect therapeutic efficacy of adoptive immunotherapy. Indeed, T-iPSC-Ts exhibit much superior proliferative capacity while retaining equivalent effector function compared to parental T-cell clones. Here, we demonstrate the methodology to produce naïve-like T-iPSC-Ts, which could be potent cell source for adoptive immunotherapy.