Kahler David J, Mellor Andrew L
Department of Medicine, Program in Molecular Immunology, Institute of Molecular Medicine and Genetics, Medical College of Georgia 1120, 15th Street, Augusta, GA 30912-2600, USA.
Handb Exp Pharmacol. 2009(188):165-96. doi: 10.1007/978-3-540-71029-5_8.
Mature dendritic cells (DCs) are potent stimulators of T cells that recognize antigens presented by the DCs. In this chapter we describe mature DCs that suppress T cell responses to antigens they present due to expression of the intracellular enzyme indoleamine 2,3 dioxygenase (IDO). IDO-competent DCs are a subset of plasmacytoid DCs that can be induced to express IDO under certain inflammatory conditions in humans and mice. Though rare, IDO-expressing DCs acquire potent T cell suppressor activity that may predominate over the T cell stimulatory functions of all other antigen-presenting cells in physiologic environments due in part, to cooperation with regulatory T cells. Thus, IDO-expressing DCs are critical regulators of adaptive immunity that contribute to a wide range of inflammatory disease processes. As such, manipulating IDO expression in DCs using IDO inhibitors or IDO inducers offers considerable opportunities to improve immunotherapies in a range of clinically-significant disease syndromes.
成熟树突状细胞(DCs)是T细胞的有效刺激物,可识别DCs呈递的抗原。在本章中,我们描述了成熟的DCs,它们由于细胞内酶吲哚胺2,3-双加氧酶(IDO)的表达而抑制T细胞对其呈递抗原的反应。具有IDO活性的DCs是浆细胞样DCs的一个亚群,在人和小鼠的某些炎症条件下可被诱导表达IDO。尽管表达IDO的DCs很少见,但它们获得了强大的T细胞抑制活性,在生理环境中,这种活性可能会超过所有其他抗原呈递细胞的T细胞刺激功能,部分原因是与调节性T细胞的协同作用。因此,表达IDO的DCs是适应性免疫的关键调节因子,参与多种炎症性疾病过程。正因如此,使用IDO抑制剂或IDO诱导剂来调控DCs中的IDO表达,为改善一系列具有临床意义的疾病综合征的免疫疗法提供了相当多的机会。