Vizcardo Raul, Rafiqul Islam S M, Maeda Takuya, Tamaoki Naritaka, Good Meghan L, Klemen Nicholas D, Bosch-Marce Marta, Jia Li, Kruhlak Mikhael J, Restifo Nicholas P
Surgery Branch, National Cancer Institute, NIH; Center for Cell-Based Therapy, National Cancer Institute, NIH;
Surgery Branch, National Cancer Institute, NIH; Center for Cell-Based Therapy, National Cancer Institute, NIH.
J Vis Exp. 2019 Aug 9(150). doi: 10.3791/58672.
The inheritance of pre-rearranged T cell receptors (TCRs) and their epigenetic rejuvenation make induced pluripotent stem cell (iPSC)-derived T cells a promising source for adoptive T cell therapy (ACT). However, classical in vitro methods for producing regenerated T cells from iPSC result in either innate-like or terminally differentiated T cells, which are phenotypically and functionally distinct from naïve T cells. Recently, a novel three-dimensional (3D) thymic culture system was developed to generate a homogenous subset of CD8αβ antigen-specific T cells with a naïve T cell-like functional phenotype, including the capacity for proliferation, memory formation, and tumor suppression in vivo. This protocol avoids aberrant developmental fates, allowing for the generation of clinically relevant iPSC-derived T cells, designated as iPSC-derived thymic emigrants (iTE), while also providing a potent tool to elucidate the subsequent functions necessary for T cell maturation after thymic selection.
预重排T细胞受体（TCR）的遗传及其表观遗传年轻化，使得诱导多能干细胞（iPSC）衍生的T细胞成为过继性T细胞疗法（ACT）的一个有前景的来源。然而，从iPSC产生再生T细胞的经典体外方法会产生固有样或终末分化的T细胞，这些细胞在表型和功能上与天然T细胞不同。最近，一种新型的三维（3D）胸腺培养系统被开发出来，以产生具有天然T细胞样功能表型的CD8αβ抗原特异性T细胞的同质亚群，包括体内增殖、记忆形成和肿瘤抑制能力。该方案避免了异常的发育命运，允许产生临床相关的iPSC衍生的T细胞，称为iPSC衍生的胸腺迁出细胞（iTE），同时还提供了一个有力的工具来阐明胸腺选择后T细胞成熟所需的后续功能。
