Immunotherapy Center & Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
Immunotherapy. 2009 Jul;1(4):645-61. doi: 10.2217/IMT.09.21.
Natural immune tolerance is a formidable barrier to successful immunotherapy to treat established cancers and chronic infections. Conversely, creating robust immune tolerance via immunotherapy is the major goal in treating autoimmune and allergic diseases, and enhancing survival of transplanted organs and tissues. In this review, we focus on a natural mechanism that creates local T-cell tolerance in many clinically relevant settings of chronic inflammation involving expression of the cytosolic enzyme indoleamine 2,3-dioxygenase (IDO) by specialized subsets of dendritic cells. IDO-expressing dendritic cells suppress antigen-specific T-cell responses directly, and induce bystander suppression by activating regulatory T cells. Thus, manipulating IDO is a promising strategy to treat a range of chronic inflammatory diseases.
天然免疫耐受是成功免疫治疗已建立的癌症和慢性感染的一个巨大障碍。相反，通过免疫治疗产生强大的免疫耐受是治疗自身免疫和过敏疾病、提高移植器官和组织存活率的主要目标。在这篇综述中，我们专注于一种天然机制，即在涉及细胞溶质酶吲哚胺 2,3-双加氧酶 (IDO) 由专门的树突状细胞亚群表达的许多与临床相关的慢性炎症情况下，在局部创建 T 细胞耐受。IDO 表达的树突状细胞直接抑制抗原特异性 T 细胞反应，并通过激活调节性 T 细胞诱导旁观者抑制。因此，操纵 IDO 是治疗一系列慢性炎症性疾病的一种很有前途的策略。
