Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15
Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15
复制标题
DOI：
10.1016/j.exphem.2008.01.001
复制
发表时间：
2008-05-01
影响因子：
2.6
通讯作者：
Miller, Jeffrey S.
中科院分区：
文献类型：
--
作者：
McCullar, Valarie;Oostendorp, Robert;Miller, Jeffrey S.
Objective.人类自然杀伤（NK）细胞成熟涉及NK细胞受体的有序获得。我们的目的是了解基质相互作用和细胞因子在这一发育过程中的重要性。将人脐血CD 34（+）/Lin（-）/CD 38（-）细胞与两种小鼠间质细胞系（AFT 024和EL 08-ID 2）进行转换培养，研究NK细胞的发育。当在不存在白细胞介素（IL）-15的情况下，在具有白细胞介素（IL）-3和FIB配体（Flt 3L）的AFT 024上培养人祖细胞时，发生NK细胞分化，尽管频率较低。这些条件有利于CD 56（-）NK细胞前体（CD 34（+）CD 7（-）、CD 34（+）CD 7（+）和CD 34（-）CD 7（+）细胞）的积累，这些细胞在成人血液A中罕见，但在新鲜UCB中丰富。在第二代培养中，IL-3或IL-3 + Flt 3L与IL-15的联合作用增加了前体细胞中CD 56（+）NK细胞的绝对数量以及CD 94和杀伤免疫球蛋白样受体（KIR）的获得。为了进一步探索NK细胞早期成熟的微环境，研究了来自小鼠胚胎肝的细胞系（EL 08-ID 2）。EL 08-ID 2的NK细胞发育和KIR获得上级EL 08-ID 2，其支持NK细胞前体的分化、NK细胞定型和增殖。虽然NK细胞成熟的最早期事件不需要外源性人IL-15，但在NK细胞定型的后期阶段需要。至少，需要鼠基质、IL-3和Flt 3L来重演早期NK细胞发育和分化成不同的NK细胞前体。EL 08 - 1D 2诱导KIR获得，表明NK细胞发育中的外源信号在小鼠和人之间是保守的。（C）2008 ISEH -血液学和干细胞学会。爱思唯尔公司出版
Objective. Human natural killer (NK) cell maturation involves the orderly acquisition of NK cell receptors. Our aim was to understand how stromal interactions and cytokines are important in this developmental process.Materials and Methods. Human umbilical cord blood (UCB) CD34(+)/Lin(-)/CD38(-) cells were cultured on two murine stromal cell lines (AFT024 and EL08-ID2) in a switch culture to study NK cell development.Results. When human progenitors were cultured on AFT024 with interleukin (IL)-3 and FIB ligand (Flt3L) in the absence of interleukin (IL)-15, NK cell differentiation occurred, albeit at low frequency. These conditions favored the accumulation of CD56(-) NK cell precursors (CD34(+)CD7(-), CD34(+)CD7(+), and CD34(-)CD7(+) cells), which are populations rare in adult blood A but abundant in fresh UCB. In secondary culture, addition of IL-3 or IL-3 + Flt3L to IL-15 increased the absolute number of CD56(+) NK cells from precursors and the acquisition of CD94 and killer immunoglobulin-like receptors (KIR). To further explore the microenvironment in early NK cell maturation, a cell line derived from murine embryonic liver (EL08-ID2) was studied. NK cell development and KIR acquisition was superior with EL08-ID2, which supported the differentiation of NK cell precursors, NK cell commitment, and proliferation.Conclusion. Although the earliest events in NK cell maturation do not require exogenous human IL-15, it is required at a later stage of NK cell commitment. At a minimum, murine stroma, IL-3, and Flt3L are required to recapitulate early NK cell development and differentiation into distinct NK cell precursors. EL08-1D2 induces KIR acquisition suggesting that extrinsic signals in NK cell development are conserved between mouse and man. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.