Comparative and Functional Evaluation of In Vitro Generated to Ex Vivo CD8 T Cells
Comparative and Functional Evaluation of In Vitro Generated to Ex Vivo CD8 T Cells
复制标题
DOI：
10.4049/jimmunol.1200979
复制
发表时间：
2012-10-01
影响因子：
4.4
通讯作者：
Zuniga-Pfluecker, Juan Carlos
中科院分区：
文献类型：
--
作者：
Dervovic, Dzana D.;Ciofani, Maria;Zuniga-Pfluecker, Juan Carlos
细胞毒性CD8 T细胞反应的产生依赖于胸腺内分化和自我耐受的限制所施加的功能结果。虽然利用OP9-DL1细胞培养可以在体外部分复制胸腺功能，从造血祖细胞中产生CD8ab TCR细胞，但对完全体外产生的来自骨髓造血干细胞的CD8T细胞的全面和功能评估尚未建立，并且仍然存在争议。在这项研究中，我们证明了体外来源的CD8T细胞的表型、分子和功能特征与体外来源的CD8T细胞相似，尽管也观察到了一些显著的差异。将体外获得的CD8T细胞转移到同基因和免疫缺陷宿主小鼠体内，没有表现出移植物抗宿主反应，而分别观察到了强劲的动态平衡增殖。这些发现，加上体外产生的CD8T细胞表达的多样化和广泛的TCR谱系，使得从完全在体外产生的CD8T细胞库中成功地获得抗原特异性T细胞。这些发现支持将抗原特异性的体外衍生效应CD8 T细胞用于免疫重建方法，这将有助于进一步定制它们用于对抗病毒感染或恶性肿瘤。免疫学杂志，2012,189：3411-3420。
The generation of the cytotoxic CD8 T cell response is dependent on the functional outcomes imposed by the intrathymic constraints of differentiation and self-tolerance. Although thymic function can be partly replicated in vitro using OP9-DL1 cell cultures to yield CD8 ab TCR-bearing cells from hematopoietic progenitor cells, a comprehensive and functional assessment of entirely in vitro generated CD8 T cells derived from bone marrow hematopoietic stem cells has not been established and remains controversial. In this study, we demonstrate that a phenotypic, molecular, and functional signature of in vitro derived CD8 T cells is akin to that of ex vivo CD8 T cells, although several significant differences were also observed. Transfer of in vitro derived CD8 T cells into syngeneic and immunodeficient host mice showed no graft-versus-host response, whereas a robust homeostatic proliferation was observed, respectively. These findings, along with a diverse and broad TCR repertoire expressed by the in vitro derived CD8 T cells, allowed for the successful generation of Ag-specific T cells to be obtained from an entirely in vitro generated CD8 T cell pool. These findings support the use of Ag-specific in vitro derived effector CD8 T cells for immune reconstitution approaches, which would be amenable to further tailoring for their use against viral infections or malignancies. The Journal of Immunology, 2012, 189: 3411-3420.