Lower concentrations of methyl-β-cyclodextrin combined with interleukin-2 can preferentially induce activation and proliferation of natural killer cells in human peripheral blood
Lower concentrations of methyl-β-cyclodextrin combined with interleukin-2 can preferentially induce activation and proliferation of natural killer cells in human peripheral blood
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DOI：
10.1016/j.humimm.2011.03.022
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发表时间：
2011-07-01
期刊：
影响因子：
2.7
通讯作者：
Li, Bai-Qing
中科院分区：
文献类型：
--
作者：
Lue, He-Zuo;Zhu, An-You;Li, Bai-Qing
先前的研究表明，高浓度的甲基-对环糊精（M β CD, 10-15 mM）可以干扰脂筏的形成并抑制淋巴细胞的激活。在本报告中，我们发现较低浓度的M β - CD （1-4 mM）可以加速人外周血单核细胞（PBMCs）淋巴细胞的增殖。扩增细胞中，CD3(-)CD56(+) NK细胞为优势亚群，NK细胞比例与M β CD浓度存在显著的剂量效应关系，3 ~ 4 mM M β CD处理组NK细胞比例达到60%以上。当PBMCs用M β - CD处理时，CD69在CD3（-）和CD56（+）细胞上比在CD3（+）细胞上更优先表达。CD25在48小时的表达没有明显差异，但当重组人白细胞介素-2 （IL-2）再添加24小时时，它也优先在NK细胞上表达。M β - CD和IL-2协同作用也能诱导CD56（+）人外周血单核细胞产生干扰素- γ (ifn - γ)。机制研究表明，M β CD + IL-2的ifn - γ产生不依赖于IL-12，但依赖于内源性IL-18和IL-1 β， CD56(+)CD14（+）树突状细胞样细胞和B细胞可能介导M β CD激活NK细胞的能力。M β cd激活的NK细胞对自然杀伤细胞敏感的K562细胞和淋巴因子激活的杀伤细胞敏感的DAUDI细胞也有很高的细胞毒性。这些研究表明，低浓度的M β - CD联合IL-2可优先诱导pbmc中NK细胞的活化和增殖。(C) 2011年美国组织相容性和免疫遗传学学会。Elsevier Inc.出版。版权所有。
Previous studies have demonstrated that high concentrations of methyl-p-cyclodextrin (M beta CD, 10-15 mM) can interfere with the formation of lipid rafts and inhibit activation of lymphocytes. In this report, we determined that lower concentrations of M beta CD) (1-4 mM) could accelerate the proliferation of lymphocytes in human peripheral blood mononuclear cells (PBMCs). In the expanded cells, CD3(-)CD56(+) natural killer (NK) cells were the dominant subpopulation, and a significant dose effect relationship existed between the proportion of NK cells and the concentration of M beta CD. In the groups treated with 3-4 mM M beta CD, the proportions of NK cells reached a level of more than 60%. When PBMCs were treated with M beta CD. CD69 was more preferentially expressed on CD3(-)CD56(+) cells than on CD3(+) cells at 48 and 72 hours. The expression of CD25 had no distinct difference at 48 hours, but when recombinant human interleukin-2 (IL-2) was added for a further 24 hours, it was also preferentially expressed on NK cells. M beta CD and IL-2 synergistically could also induce interferon-gamma (IFN-gamma) production in CD56(+) human PBMCs. Mechanistic studies revealed that IFN-gamma production in response to M beta CD plus IL-2 was IL-12 independent but depended on endogenous IL-18 and IL-1 beta, and CD56(+)CD14(+) dendritic cell-like cells and B cells might mediate the ability of M beta CD to activate NK cells. The M beta CD-activated NK cells also had high cytotoxicity against the natural killer cell sensitive K562 cells or lymphokine-activated killer cell sensitive DAUDI cells in vitro. These studies indicated that lower concentrations of M beta CD combined with IL-2 can preferentially induce activation and proliferation of NK cells in PBMCs. (C) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.