Genetically manipulated human embryonic stem cell-derived dendritic cells with immune regulatory function
Genetically manipulated human embryonic stem cell-derived dendritic cells with immune regulatory function
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DOI：
10.1634/stemcells.2007-0321
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发表时间：
2007-11-01
期刊：
影响因子：
5.2
通讯作者：
Nishimura, Yasuharu
中科院分区：
文献类型：
--
作者：
Senju, Satoru;Zembutsu, Hitoshi;Nishimura, Yasuharu
基因修饰的树突状细胞（DC）被认为是一种很有前途的抗原特异性免疫治疗手段。本研究报告了从人胚胎干细胞（ES）来源的DC的产生、表征和遗传修饰。人ES细胞来源的DC（ES-DC）表达DC典型表达的表面分子，并具有刺激同种异体T淋巴细胞的能力，以及在组织相容性白细胞抗原（HLA）11类分子的背景下加工和呈递蛋白抗原的能力。人ES-DC的遗传修饰可以在不使用病毒载体的情况下完成，通过电穿孔将表达载体质粒引入未分化的ES细胞中，随后诱导转染的ES细胞克隆分化为ES-DC。通过这种方法引入基于不变链的抗原呈递载体的ES-DC在缺乏外源抗原的情况下刺激HLA-DR限制性抗原特异性T细胞。程序性死亡1配体1在ES-DC中的强制表达导致与ES-DC共培养的同种异体T细胞的增殖反应降低。通过目前建立的方法，也实现了从非人灵长类（食蟹猴）ES细胞产生和遗传修饰ES-DC。因此，ES-DC技术被认为是一种新的免疫治疗手段。
Genetically manipulated dendritic cells (DC are considered to be a promising means for antigen-specific immune therapy. This study reports the generation, characterization, and genetic modification of DC derived from human embryonic stem (ES) cells. The human ES cell-derived DC (ES-DC expressed surface molecules typically expressed by DC and had the capacities to stimulate allogeneic T lymphocytes and to process and present protein antigen in the context of histocompatibility leukocyte antigen (HLA) class 11 molecule. Genetic modification of human ES-DC can be accomplished without the use of viral vectors, by the introduction of expression vector plasmids into undifferentiated ES cells by electroporation and subsequent induction of differentiation of the transfectant ES cell clones to ES-DC. ES-DC introduced with invariant chain-based antigen-presenting vectors by this procedure stimulated HLA-DR-restricted antigen-specific T cells in the absence of exogenous antigen. Forced expression of programmed death-1-ligand-1 in ES-DC resulted in the reduction of the proliferative response of allogeneic T cells cocultured with the ES-DC. Generation and genetic modification of ES-DC from nonhuman primate (cynomolgus monkey) ES cells was also achieved by the currently established method. ES-DC technology is therefore considered to be a novel means for immune therapy.