A novel myeloid-like NK cell progenitor in human umbilical cord blood
A novel myeloid-like NK cell progenitor in human umbilical cord blood
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DOI：
10.1182/blood-2002-05-1501
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发表时间：
2003-05-01
期刊：
影响因子：
20.3
通讯作者：
Papamichail, M
中科院分区：
文献类型：
--
作者：
Perez, SA;Sotiropoulou, PA;Papamichail, M
自然杀伤(NK)细胞从多能的CD34(+)人造血干细胞或少潜能的淋巴祖细胞分化而来的报道已经被报道。本研究用Flt3配体(FL)和白介素15(IL-15)建立了脐带血CD56(-)/CD34(-)髓样贴壁细胞(ACF)的长期培养，其特征是表达CD14(+)和其他髓系标志。UCB/ACF逐渐表达CD56标志物，至第15天达到相当高的水平(约90%的细胞为CD56(+))。FL+IL-15驱动的ACF/CD56(+)细胞逐渐表达成熟的NK功能程序，在IL-12和IL-18刺激下，同时裂解NK和淋巴因子激活的杀伤(LAK)敏感的肿瘤靶点，并产生高水平的干扰素-γ(干扰素-γ)、粒-巨噬细胞集落刺激因子、肿瘤坏死因子-α和IL-10。高纯度的脐血CD14(+)细胞与FL和IL-15共同培养也得到了类似的结果。相反，在相同条件下培养的UCB/CD34(+)细胞表现出CD56的延迟表达，并且表现出不同的功能，它们具有NK而不是LAK细胞毒作用，并且产生的细胞因子显著减少。对加入FL和IL-15的UCB/ACF或UCB/CD14(+)细胞表型的动力学研究显示，CD14的表达在第5天后迅速下降，到第20天达到零水平。到第5天，大约60%的CD56(+)来源于UCB/ACF或UCB/CD14(+)细胞共表达CD14。综上所述，我们的数据支持CD14(+)髓样细胞作为一种新的淋巴样NK细胞的作用。(C)2003年，由美国血液病学会提供。
Natural killer (NK) cell differentiation from pluripotent CD34(+) human hematopoietic stem cells or oligopotent lymphoid progenitors has already been reported. In the present study, long-term cultures of the CD56(-)/CD34(-) myeloid-like adherent cell fraction (ACF) from umbilical cord blood (UCB), characterized by the expression of CD14(+) as well as other myeloid markers, were set up with flt3 ligand (FL) and interleukin-15 (IL-15). The UCB/ACF gradually expressed the CD56 marker, which reached fairly high levels (approximately 90% of the cells were CD56(+)) by day 15. FL plus IL-15-driven ACF/CD56(+) cells progressively expressed a mature NK functional program lysing both NK- and lymphokine-activate killer (LAK)sensitive tumor targets and producing high levels of interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and IL-10 upon stimulation with IL-12 and IL-18. Similar results were obtained when highly purified CD14(+) cells from UCB were cultured with FL and IL-15. In contrast, UCB/CD34(+) cells cultured under the same conditions showed a delayed expression of CD56 and behaved functionally differently in that they exhibited NK but not LAK cytotoxicity and produced significantly fewer cytokines. Kinetic studies on the phenotype of UCB/ACF or UCB/CD14(+) cells cultured in the presence of FL and IL-15 showed a rapid decrease in CD14 expression after day 5, which reached levels of zero by day 20. Approximately 60% of the CD56(+) derived from the UCB/ACF or the UCB/CD14(+) cells coexpressed CD14 by day 5. Taken together, our data support the role of CD14(+) myeloid-like cells within UCB as a novel progenitor for lymphoid NK cells. (C) 2003 by The American Society of Hematology.