In vitro induction of natural killer T cells from embryonic stem cells prepared using somatic cell nuclear transfer
In vitro induction of natural killer T cells from embryonic stem cells prepared using somatic cell nuclear transfer
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DOI：
10.1096/fj.07-104687
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发表时间：
2008-07-01
期刊：
影响因子：
4.8
通讯作者：
Fujita, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Wakao, Hiroshi;Wakao, Rika;Fujita, Hiroyoshi
Notch受体配体δ样1在基质细胞上的异位表达允许从胚胎干细胞（ESCs）诱导T细胞。然而，这些体外生成的T细胞不能移植，因为它们太不成熟，无法在免疫功能低下的动物体内产生免疫反应。我们利用体细胞核移植（somatic cell nuclear transfer, ntESCs）技术，从外周iNKT细胞衍生的ESCs中有效地生成了一个称为不变自然杀伤T （iNKT）细胞的T细胞子集。这些iNKT细胞在体内自主成熟，并以抗原特异性的方式表现出伴随干扰素- γ产生的辅助作用。这种辅助作用最终抑制了接种肿瘤细胞的生长。我们的研究结果表明，ntesc衍生的iNKT细胞是可移植的淋巴细胞，有助于诱导免疫耐受和治疗自身免疫性疾病、肿瘤和感染。
The ectopic expression of the Notch receptor ligand delta-like 1 on stromal cells allows the induction of T cells from embryonic stem cells (ESCs). However, these in vitro-generated T cells are not transplantable because they are too immature to mount an immune response in an immunocompromised animal. We efficiently generated a subset of T cells called invariant natural killer T (iNKT) cells from ESCs derived from peripheral iNKT cells using somatic cell nuclear transfer (ntESCs). These iNKT cells matured autonomously in vivo and exhibited an adjuvant effect accompanying the production of interferon-gamma in an antigen-specific manner. This adjuvant effect culminated in the inhibition of inoculated tumor cell growth. Our results indicate that ntESC-derived iNKT cells are transplantable lymphocytes that will be beneficial for the induction of immune tolerance and the treatment of autoimmune diseases, tumors, and infections.