Production of IL-5 by human NK cells and regulation of IL-5 secretion by IL-4, IL-10, and IL-12.
Production of IL-5 by human NK cells and regulation of IL-5 secretion by IL-4, IL-10, and IL-12.
复制标题
人类 NK 细胞产生 IL-5，并通过 IL-4、IL-10 和 IL-12 调节 IL-5 分泌。
DOI：
10.4049/jimmunol.154.10.5144
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发表时间：
1995
影响因子：
4.4
通讯作者：
L. Lanier
中科院分区：
文献类型：
--
作者：
H. Warren;B. Kinnear;J. Phillips;L. Lanier
当用易感靶细胞刺激或通过CD 16和CD 94细胞表面分子刺激时，人NK细胞产生IFN-γ、TNF-α和粒细胞巨噬细胞-CSF。这项研究报告说，NK细胞也产生IL-5，一种细胞因子，通常由Th 2细胞产生，介导动员和嗜酸性粒细胞的分化。多克隆NK细胞群和NK细胞克隆在用γ-辐照的MM-170黑素瘤细胞或JY B-淋巴母细胞样细胞和rIL-2刺激增殖时产生IL-5。IL-5在由新鲜分离的NK细胞产生的培养物（原代培养物）中产生，并且当来自原代培养物的静止NK细胞被再刺激以增殖时（二次培养物）产生。与初级培养物相比，次级培养物中IL-5的产生平均高8.8倍（n > 18），表明NK细胞产生IL-5的能力在初级刺激期间成熟。IL-5分泌，特别是在原代培养物中，被IL-4增强，并被IL-12和IL-10抑制。相比之下，IL-4和IL-12对IFN-γ分泌具有相反的作用。不再分泌细胞因子的培养的NK细胞可以用佛波醇12，13二丁酸酯和离子霉素或在rIL-2存在下用易感靶细胞再刺激。这些培养物中的IL-5产生仅在NK细胞处于指数生长期时发生，而IFN-γ、TNF-α和粒细胞巨噬细胞-CSF也通过刺激静止细胞产生，尽管程度较低。此外，细胞因子的产生与NK细胞的细胞溶解活性无关。总之，增殖的人NK细胞具有产生IL-5的潜力，其分泌受IL-4、IL-10和IL-12调节。
Human NK cells produce IFN-gamma, TNF-alpha, and granulocyte macrophage-CSF when stimulated with susceptible target cells or through the CD16 and CD94 cell surface molecules. This study reports that NK cells also produce IL-5, a cytokine typically produced by Th2 cells, which mediates mobilization and differentiation of eosinophils. Polyclonal NK cell populations and NK cell clones produce IL-5 when stimulated to proliferate with gamma-irradiated MM-170 melanoma cells or JY B-lymphoblastoid cells and rIL-2. IL-5 is produced in cultures generated from freshly isolated NK cells (primary cultures) and when quiescent NK cells from primary cultures are restimulated to proliferate (secondary cultures). Production of IL-5 is on average 8.8-fold greater in secondary cultures compared with primary cultures (n > 18), suggesting that the ability of NK cells to produce IL-5 matures during primary stimulation. IL-5 secretion, particularly in primary cultures, is augmented by IL-4 and is inhibited by IL-12 and IL-10. By contrast, IL-4 and IL-12 have the reverse effects on IFN-gamma secretion. Cultured NK cells that no longer secrete cytokines can be restimulated to do so with either phorbol 12, 13 dibutyrate and ionomycin or with susceptible target cells in the presence of rIL-2. IL-5 production in these cultures occurs only when NK cells are in an exponential growth phase, whereas IFN-gamma, TNF-alpha, and granulocyte macrophage-CSF are produced also by stimulation of quiescent cells, although to a lesser extent. Furthermore, cytokine production is unrelated to the cytolytic activity of NK cells. In conclusion, proliferating human NK cells have the potential to produce IL-5 with secretion regulated by IL-4, IL-10, and IL-12.