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Ex Vivo Generated Natural Killer Cells Acquire Typical Natural Killer Receptors and Display a Cytotoxic Gene Expression Profile Similar to Peripheral Blood Natural Killer Cells

机译：体内生成的自然杀伤细胞获得典型的自然杀伤受体并显示类似于外周血自然杀伤细胞的细胞毒性基因表达谱

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Ex vivo differentiation systems of natural killer (NK) cells from CD34⁺ hematopoietic stem cells are of potential importance for adjuvant immunotherapy of cancer. Here, we analyzed ex vivo differentiation of NK cells from cord blood-derived CD34⁺ stem cells by gene expression profiling, real-time RT-PCR, flow cytometry, and functional analysis. Additionally, we compared the identified characteristics to peripheral blood (PB) CD56^bright and CD56^dim NK cells. The data show sequential expression of CD56 and the CD94 and NKG2 receptor chains during ex vivo NK cell development, resulting finally in the expression of a range of genes with partial characteristics of CD56^bright and CD56^dim NK cells from PB. Expression of characteristic NK cell receptors and cytotoxic genes was mainly found within the predominant ex vivo generated population of NKG2A⁺ NK cells, indicating the importance of NKG2A expression during NK cell differentiation and maturation. Furthermore, despite distinct phenotypic characteristics, the detailed analysis of cytolytic genes expressed within the ex vivo differentiated NK cells revealed a pattern close to CD56^dim NK cells. In line with this finding, ex vivo generated NK cells displayed potent cytotoxicity. This supports that the ex vivo differentiation system faithfully reproduces major steps of the differentiation of NK cells from their progenitors, constitutes an excellent model to study NK cell differentiation, and is valuable to generate large-scale NK cells appropriate for immunotherapy.

机译：CD34 ^{+ 造血干细胞对自然杀伤（NK）细胞的体外分化系统对于癌症的辅助免疫治疗具有潜在的重要性。在这里，我们通过基因表达谱分析，实时RT-PCR，流式细胞术和功能分析，分析了NK细胞从脐血来源的CD34 ^{+ 干细胞的离体分化。另外，我们将鉴定出的特征与外周血（PB）CD56 ^{bright 和CD56 ^{dim NK细胞进行了比较。数据显示离体NK细胞发育过程中CD56以及CD94和NKG2受体链的顺序表达，最终导致一系列具有CD56 ^{bright 和CD56 ^{dim部分特征的基因表达 PB的NK细胞。主要在离体产生的主要NKG2A ^{+ NK细胞群体中发现特征性NK细胞受体和细胞毒性基因的表达，这表明NKG2A表达在NK细胞分化和成熟中的重要性。此外，尽管具有明显的表型特征，但对离体分化的NK细胞内表达的溶细胞基因的详细分析显示，其模式接近CD56 ^{dim NK细胞。与该发现一致，离体产生的NK细胞显示出强的细胞毒性。这支持离体分化系统忠实地再现了NK细胞从其祖细胞分化的主要步骤，构成了研究NK细胞分化的优秀模型，并且对于生成适合于免疫疗法的大规模NK细胞非常有价值。}}}}}}}}

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期刊名称 Stem Cells and Development
作者
Dorit Lehmann; Jan Spanholtz; Markus Osl; Marleen Tordoir; Karoline Lipnik; Martin Bilban; Bernhard Schlechta; Harry Dolstra; Erhard Hofer;
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年(卷),期 -1(21),16
年度 -1
页码 2926–2938
总页数 13
原文格式 PDF
正文语种
中图分类医学史;血液学检验;移植;
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专利

1. Ex vivo generated natural killer cells acquire typical natural killer receptors and display a cytotoxic gene expression profile similar to peripheral blood natural killer cells [J] . LehmannD., SpanholtzJ., OslM., Stem cells and development . 2012,第16期

机译：离体产生的自然杀伤细胞获得典型的自然杀伤受体，并显示类似于外周血自然杀伤细胞的细胞毒性基因表达谱
2. Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural killer cells in pregnant women with a history of recurrent pregnancy loss [J] . Fukui Atsushi, Funamizu Ayano, Fukuhara Rie, The journal of obstetrics and gynaecology research . 2017,第11期

机译：具有复发性妊娠损失或植入失效的妇女子宫内膜自然杀伤细胞对孕妇子宫内膜自然杀伤细胞的表达，以及复发性妊娠病史患有孕妇外周血自然杀伤细胞的天然细胞毒性受体
3. Expression patterns of lectin-like natural killer receptors, inhibitory CD94/NKG2A, and activating CD94/NKG2C on decidual CD56bright natural killer cells differ from those on peripheral CD56dim natural killer cells. [J] . Kusumi M, Yamashita T, Fujii T, Journal of Reproductive Immunology . 2006,第1a2期

机译：蜕膜凝集素样自然杀伤受体的表达模式，抑制性CD94 / NKG2A和活化CD94 / NKG2C在蜕膜CD56bright自然杀伤细胞上的表达方式与外周CD56dim自然杀伤细胞上的表达方式不同。
4. The Number of Natural Killer Cells and Their Membrane Immunoglobulin - Like Receptor Decreased in the Peripheral Blood in Patients with Severe Acute Respiratory Syndrome [C] . Wang Chen, Xia Chengqing Proceedings of International Science Symposium on SARS . 2003

机译：严重急性呼吸系统综合症患者外周血中自然杀伤细胞数量及其膜免疫球蛋白样受体的减少
5. gammadelta T cells derived from peripheral blood and cerebrospinal fluid of multiple sclerosis patients: Cytotoxic mechanisms, inhibitory natural killer cell receptors, and protein analysis. [D] . Green, Melanie Leslie Dawn. 2005

机译：多发性硬化症患者外周血和脑脊液中产生的γT细胞：细胞毒性机制，抑制性自然杀伤细胞受体和蛋白质分析。
6. Expression of different lipoprotein receptors in natural killer cells and their effect on natural killer proliferative and cytotoxic activity. [O] . J B De Sanctis, I Blanca, N E Bianco 1995

机译：不同脂蛋白受体在自然杀伤细胞中的表达及其对自然杀伤细胞增殖和细胞毒性活性的影响。
7. Ex Vivo Generated Natural Killer Cells Acquire Typical Natural Killer Receptors and Display a Cytotoxic Gene Expression Profile Similar to Peripheral Blood Natural Killer Cells [O] . Dorit Lehmann, Jan Spanholtz, Markus Osl, 2012

机译：exvivo产生的天然杀手细胞获得典型的自然杀伤受体，并显示与外周血自然杀伤细胞相似的细胞毒性基因表达谱

Ex Vivo Generated Natural Killer Cells Acquire Typical Natural Killer Receptors and Display a Cytotoxic Gene Expression Profile Similar to Peripheral Blood Natural Killer Cells

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