Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells.
Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells.
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DOI：
10.4049/jimmunol.154.10.5071
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发表时间：
1995-05
影响因子：
4.4
通讯作者：
S. Macatonia;N. Hosken;M. Litton;P. Vieira;C. Hsieh;J. Culpepper;M. Wysocka;G. Trinchieri;K. Mur
中科院分区：
文献类型：
--
作者：
S. Macatonia;N. Hosken;M. Litton;P. Vieira;C. Hsieh;J. Culpepper;M. Wysocka;G. Trinchieri;K. Mur
树突状细胞是APC，其在体外和体内刺激初级Ag特异性反应的增殖的效力是独特的。在这项研究中，我们证明了树突状细胞可以产生IL-12，一种主要的细胞因子参与IFN-γ产生T细胞的发展。这一发现源于我们的观察，即在中和内源性IL-4水平后，树突状细胞诱导的来自总CD 4 + T细胞的Th 1发育是IL-12依赖性的。此外，我们证明，树突状细胞可以诱导发展的Th 1细胞从Ag-特异性幼稚LECAM-1明亮的CD 4 + T细胞从α β-TCR转基因小鼠，提供的CD 4 + LECAM-1迟钝的T细胞，产生显着水平的IL-4，不存在于原代培养。树突状细胞产生IL-12通过用特异于诱导型IL-12 p40亚基的Ab进行阳性免疫荧光染色来证实。这表明，除了诱导幼稚T细胞的增殖和克隆扩增之外，树突状细胞通过其IL-12的产生在IFN-γ产生细胞的发育中发挥直接作用，所述IFN-γ产生细胞对于细胞介导的免疫应答是重要的。
Dendritic cells are APCs that are unique in their potency to stimulate proliferation of primary Ag-specific responses in vitro and in vivo. In this study, we demonstrate that dendritic cells can produce IL-12, a dominant cytokine involved in the development of IFN-gamma-producing T cells. This finding resulted from our observations that dendritic cell-induced Th1 development from total CD4+ T cells upon neutralization of endogenous levels of IL-4 was IL-12-dependent. Furthermore, we demonstrate that dendritic cells can induce the development of Th1 cells from Ag-specific naive LECAM-1bright CD4+ T cells obtained from alpha beta-TCR transgenic mice, provided that CD4+ LECAM-1dull T cells, which produce significant levels of IL-4, are not present in the primary cultures. Production of IL-12 by dendritic cells was confirmed by positive immunofluoresence staining with Abs specific for the inducible IL-12 p40 subunit. This suggests that in addition to inducing proliferation and clonal expansion of naive T cells, dendritic cells, by their production of IL-12, play a direct role in the development of IFN-gamma-producing cells that are important for cell-mediated immune responses.