| Efficient Production of Functional Human NKT Cells from Induced Pluripotent Stem Cells − Reprogramming of Human Vα24+iNKT Cells
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Author:
Date:
2017-05-20
[Abstract] Antigen-specific T cell-derived induced pluripotent stem cells (iPSCs) have been shown to re-differentiate into functional T cells and thus provide a potential source of T cells that could be useful for cancer immunotherapy. Human Vα24+ invariant natural killer T (Vα24+iNKT) cells are subset of T cells that are characterized by the expression of an invariant Vα24-Jα18 paired with Vβ11, that recognize glycolipids, such as α-galactosylceramide (α-GalCer), presented by the MHC class I-like molecule CD1d. Vα24+iNKT cells capable of producing IFN-γ are reported to ...
[摘要] 抗原特异性T细胞来源的诱导多能干细胞（iPSCs）已显示重新分化为功能性T细胞，从而提供可用于癌症免疫治疗的T细胞的潜在来源。不变性自然杀伤T（Vα24 + iNKT）细胞的人Vα24 + 细胞是T细胞的子集，其特征在于与Vβ11配对的不变Vα24-Jα18的表达，其识别糖脂，如α-半乳糖神经酰胺（α-GalCer），由MHC I类分子CD1d呈递。据报道能够产生IFN-γ的Vα24 + i / KT细胞增加抗肿瘤反应，其影响NK细胞和CD8 +细胞毒性T淋巴细胞以消除MHC - 和MHC + 肿瘤细胞。在这里，我们描述了将人Vα24 + iNKT细胞重编程到iPSC中的鲁棒方案，然后将其重新分化为Vα24 + iNKT细胞（iPS-Vα24功能的iNKT）。我们进一步提供了测定iPS-Vα24 + iNKT细胞活性的方案。背景 以前有报道说，针对晚期非小细胞肺癌（NSCLC）和头颈部癌症的Vα24 + iNKT细胞癌免疫治疗的临床试验显示疗效，耐受性良好（Motohashi et al。等人，2009; Yamasaki等人，2011）。然而，已知来自外周血单核细胞（PBMC）的Vα24 ...
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| Generation of Human iNKT Cell Lines
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Author:
Date:
2013-03-20
[Abstract] Natural killer T (NKT) cells comprise an important immunoregulatory T cell subset and express cell surface proteins characteristic of both natural killer cells and T cells. Invariant NKT (iNKT) cells are activated by lipid antigen presented in the context of CD1d molecules, in contrast to classic T cell subsets which recognize peptide antigens presented by MHC molecules. Following activation, iNKT cells rapidly secrete large amounts of cytokines and can lyse tumor cells and virally infected cells; however, iNKT cells are reduced in patients with autoimmune disease and cancer. The potential ...
[摘要] 自然杀伤T（NKT）细胞包含重要的免疫调节T细胞亚群，并表达天然杀伤细胞和T细胞特有的细胞表面蛋白。与识别由MHC分子呈递的肽抗原的经典T细胞亚群形成对比，不变NKT（iNKT）细胞被在CD1d分子的环境中存在的脂质抗原活化。激活后，iNKT细胞快速分泌大量细胞因子，并且可以裂解肿瘤细胞和病毒感染的细胞;然而，iNKT细胞在患有自身免疫性疾病和癌症的患者中减少。表征和研究iNKT细胞用于治疗目的的前瞻性用途的潜力随着刺激和扩增人iNKT细胞的能力而显着增加。在这个协议，我们描述一种生成和传播原代人类iNKT细胞的方法。具体地，从人外周血单核细胞（PBMC）分离初级iNKT细胞，然后在人IL-2存在下用照射的α-GalCer负载的自体未成熟树突细胞（DC）定期扩增。
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