Expansion of Functional Human Mucosal-Associated Invariant T Cells via Reprogramming to Pluripotency and Redifferentiation
Expansion of Functional Human Mucosal-Associated Invariant T Cells via Reprogramming to Pluripotency and Redifferentiation
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DOI：
10.1016/j.stem.2013.03.001
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发表时间：
2013-05-02
期刊：
影响因子：
23.9
通讯作者：
Fujita, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Wakao, Hiroshi;Yoshikiyo, Kazunori;Fujita, Hiroyoshi
粘膜相关不变T细胞（MAIT）在宿主病原体防御中发挥重要的生理作用，也可能参与炎症性疾病和多发性硬化症。这些细胞的稀少和低效的扩增阻碍了详细的分析和应用。在这里，我们报告了一种基于诱导多能干细胞（iPSC）的重编程方法，用于功能性MAIT细胞的扩增。我们发现人类MAIT细胞可以使用携带标准重编程因子的仙台病毒重编程为iPSC。在T细胞允许的条件下，这些iPSC有效地再分化成表达T细胞受体V α 7.2、CD 161和白细胞介素-18受体链α的MAIT样淋巴细胞。在与细菌饲养的单核细胞孵育后，衍生的MAIT细胞显示出广泛的细胞因子的产生增强。过继转移到免疫功能低下的小鼠后，这些细胞迁移到骨髓、肝脏、脾脏和肠道，并保护免受结核分枝杆菌的侵害。我们的研究结果为MAIT细胞的进一步功能分析和确定其治疗潜力铺平了道路。
Mucosal-associated invariant T (MAIT) cells play an important physiological role in host pathogen defense and may also be involved in inflammatory disorders and multiple sclerosis. The rarity and inefficient expansion of these cells have hampered detailed analysis and application. Here, we report an induced pluripotent stem cell (iPSC)-based reprogramming approach for the expansion of functional MAIT cells. We found that human MAIT cells can be reprogrammed into iPSCs using a Sendai virus harboring standard reprogramming factors. Under T cell-permissive conditions, these iPSCs efficiently redifferentiate into MAIT-like lymphocytes expressing the T cell receptor V alpha 7.2, CD161, and interleukin-18 receptor chain alpha. Upon incubation with bacteria-fed monocytes, the derived MAIT cells show enhanced production of a broad range of cytokines. Following adoptive transfer into immunocompromised mice, these cells migrate to the bone marrow, liver, spleen, and intestine and protect against Mycobacterium abscessus. Our findings pave the way for further functional analysis of MAIT cells and determination of their therapeutic potential.