High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.
High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.
复制标题
DOI：
10.1084/jem.184.2.741
复制
发表时间：
1996-08-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
我们以前已经证明，树突状细胞(DC)在与CD4+T细胞相互作用时产生IL-12。在这里，我们问的是这种IL-12的产生是如何诱导和调节的。用定量聚合酶链式反应和原位杂交法检测IL-12p40的表达，并用酶联免疫吸附试验检测p70异源二聚体的表达。我们证明，CD40或MHC II类分子的连接独立地触发DC产生IL-12，并且IL-4和IL-10下调了IL-12的产生。抗CD40单抗或T细胞杂交瘤细胞可在72 h内由1×10(6)DC产生260-4700pg/ml的IL-12。CD40介导的途径表明，即使在没有同源抗原识别的情况下，DC在与活化的表达CD40配体的辅助T细胞相互作用时也能诱导IL-12的产生。IL-12产生的并列比较和使用抗CD40配体单抗的阻断实验表明，CD40介导的途径在数量上比通过MHC II类分子诱导更重要。CD40/CD40配体相互作用在DC诱导IL-12中的重要性可能是最近发现缺乏CD40配体的小鼠在建立Th1型细胞免疫应答方面受到损害的原因之一。
We have shown previously that dendritic cells (DC) produce IL-12 upon interaction with CD4+ T cells. Here we ask how this IL-12 production is induced and regulated. Quantitative PCR and in situ hybridization for IL-12 p40 and an ELISA specific for the p70 heterodimer were used to determine IL-12 production. We demonstrate that ligation of either CD40 or MHC class II molecules independently trigger IL-12 production in DC, and that IL-12 production is downregulated by IL-4 and IL-10. The levels of bioactive IL-12 that can be released by triggering with an anti-CD40 mAb or with a T cell hybridoma are high (range 260-4700 pg/ml from 1 X 10(6) DC in 72 h). The CD40-mediated pathway indicates that IL- 12 production is induced in DC upon interaction with activated, CD40 ligand-expressing helper T cells, even in the absence of cognate antigen recognition. Side-by-side comparison of IL-12 production, and blocking experiments employing an anti-CD40 ligand mAb, suggest that the CD40-mediated pathway is quantitatively more significant than induction via the MHC class II molecule. The importance of the CD40/CD40 ligand interaction for IL-12 induction in DC likely contributes to the recent finding that mice lacking the CD40 ligand are impaired in mounting Th1 type cell-mediated immune responses.