Chen Luqiu, Grabowski Kristy A, Xin Jun-Ping, Coleman John, Huang Zan, Espiritu Baltazar, Alkan Serhan, Xie H Bill, Zhu Yuechun, White Fletcher A, Clancy John, Huang Hua
Department of Cell Biology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
J Immunol. 2004 Feb 15;172(4):2059-66. doi: 10.4049/jimmunol.172.4.2059.
Innate effector cells that produce Th2-type cytokines are critical in Th2 cell-mediated immune responses. However, it is not known how these cells acquire the ability to produce Th2 cytokines. IL-4 is a potent inducer that directs differentiation of naive CD4(+) T cells into CD4(+) Th2 effector cells. To determine whether IL-4 can induce differentiation and expansion of Th2 cytokine-producing innate cells, we used mice whose il-4 gene was replaced by a knock-in green fluorescence protein (gfp) gene. We found that, directly ex vivo, IL-4 increased the number of GFP(+) cells in the airway and the lung tissue in an Ag-specific manner. The majority of GFP(+) cells were eosinophils, suggesting that IL-4 plays a pivotal role in expanding IL-4-producing eosinophils in vivo. IL-4-producing eosinophils showed some unique features compared with IL-4-producing CD4(+) T cells. They exhibited biallelic expression of the il-4 gene when stimulated and were more dominant IL-4- and IL-5-producing cells. Furthermore, we show that IL-4 drove bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils in vitro. These results strongly suggest IL-4 is a potent factor in directing bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils.
产生Th2型细胞因子的固有效应细胞在Th2细胞介导的免疫反应中至关重要。然而，目前尚不清楚这些细胞如何获得产生Th2细胞因子的能力。白细胞介素-4（IL-4）是一种有效的诱导剂，可引导未成熟的CD4(+) T细胞分化为CD4(+) Th2效应细胞。为了确定IL-4是否能诱导产生Th2细胞因子的固有细胞的分化和扩增，我们使用了il-4基因被敲入绿色荧光蛋白（gfp）基因取代的小鼠。我们发现，直接在体外，IL-4以抗原特异性方式增加了气道和肺组织中GFP(+)细胞的数量。大多数GFP(+)细胞是嗜酸性粒细胞，这表明IL-4在体内扩增产生IL-4的嗜酸性粒细胞中起关键作用。与产生IL-4的CD4(+) T细胞相比，产生IL-4的嗜酸性粒细胞表现出一些独特的特征。它们在受到刺激时表现出il-4基因的双等位基因表达，并且是更主要的产生IL-4和IL-5的细胞。此外，我们表明IL-4在体外驱动骨髓祖细胞分化为产生Th2细胞因子的嗜酸性粒细胞。这些结果强烈表明IL-4是引导骨髓祖细胞分化为产生Th2细胞因子的嗜酸性粒细胞的有效因子。
