Molecular mechanism and function of CD40/CD40L engagement in the immune system.
Molecular mechanism and function of CD40/CD40L engagement in the immune system.
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DOI：
10.1111/j.1600-065x.2009.00782.x
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发表时间：
2009-05
影响因子：
8.7
通讯作者：
Noelle RJ
中科院分区：
文献类型：
--
作者：
Elgueta R;Benson MJ;de Vries VC;Wasiuk A;Guo Y;Noelle RJ
在产生成功的适应性免疫应答过程中，需要多种分子信号。主要信号是同源抗原与T淋巴细胞和B淋巴细胞表达的抗原受体结合。多个次级信号涉及T淋巴细胞和B淋巴细胞表达的共刺激分子与其各自的配体的参与。由于其在免疫中的重要作用，最具特征的共刺激分子之一是受体CD40。该受体是肿瘤坏死因子受体家族的一员，在B细胞、专业抗原呈递细胞以及非免疫细胞和肿瘤中均有表达。CD40与其配体CD40L结合，在炎症条件下，CD40L在T细胞和其他非免疫细胞上短暂表达。CD40参与调控了广泛的分子和细胞过程，包括细胞和体液适应性免疫的启动和进展。在这篇综述中，我们描述了由CD40启动的下游信号通路，并概述了CD40参与或拮抗如何调节体液和细胞免疫。最后，我们讨论了CD40作为靶点在抗肿瘤免疫中的作用。这一综述强调了CD40在适应性免疫中的重要作用。
During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.