Detournay Olivier, Mazouz Naima, Goldman Michel, Toungouz Michel
Department of Immunology-Hematology-Transfusion, Erasme Hospital, Brussels, Belgium.
Hum Immunol. 2005 May;66(5):460-8. doi: 10.1016/j.humimm.2005.01.012. Epub 2005 Feb 26.
The dendritic cell family is composed of different subsets differentially governing the immune response. Type I interferon (IFN) dendritic cells (DC) are endowed with the ability to trigger both Th1 and Th2 type responses. In view of the pivotal role of regulatory T cells in limiting the effectiveness of effector cells, we analyzed the interactions between these cells and type I IFN DC. DC were generated from monocytes in the presence of IFN-beta and interleukin (IL)-3 (DCI3) or granulocyte macrophage-colony-stimulating factor and IL-4 (DCG4) and activated by poly(I:C). Despite the release of lower amounts of IL-12 after maturation, DCI3 were able to induce a higher IFN-gamma production by T lymphocytes during the mixed leucocyte reaction (MLR) as compared with DCG4. mRNA analysis disclosed that DCI3 overtranscribed the IL-6 gene and secreted high amounts of the protein. Neutralization of IL-6 revealed that this cytokine specifically contributed to the IFN-gamma release induced by DCI3. Finally, depletion of CD25+ T cells before the MLR identified these cells as a target for IL-6. We conclude that DCI3 are endowed with the property of regulating the suppressive effect of regulatory T cells through high IL-6 production. This novel mechanism of T cell control is relevant for the use of DCI3 in vaccination strategies.
树突状细胞家族由不同的亚群组成，这些亚群对免疫反应的调控各不相同。I型干扰素（IFN）树突状细胞（DC）具有触发Th1和Th2型反应的能力。鉴于调节性T细胞在限制效应细胞有效性方面的关键作用，我们分析了这些细胞与I型IFN DC之间的相互作用。DC由单核细胞在IFN-β和白细胞介素（IL）-3（DCI3）或粒细胞巨噬细胞集落刺激因子和IL-4（DCG4）存在的情况下产生，并通过聚肌胞苷酸（poly(I:C)）激活。尽管成熟后IL-12释放量较低，但与DCG4相比，DCI3在混合淋巴细胞反应（MLR）期间能够诱导T淋巴细胞产生更高水平的IFN-γ。mRNA分析显示，DCI3过度转录IL-6基因并分泌大量该蛋白。IL-6的中和作用表明，这种细胞因子对DCI3诱导的IFN-γ释放有特异性贡献。最后，在MLR之前耗尽CD25+ T细胞，确定这些细胞是IL-6的作用靶点。我们得出结论，DCI3具有通过高表达IL-6来调节调节性T细胞抑制作用的特性。这种新型的T细胞控制机制与DCI3在疫苗接种策略中的应用相关。
