van Kooten C, Banchereau J
Department of Nephrology, Leiden University Medical Center, The Netherlands.
J Leukoc Biol. 2000 Jan;67(1):2-17. doi: 10.1002/jlb.67.1.2.
CD40 is a cell surface receptor that belongs to the tumor necrosis factor-R (TNF-R) family, and that was first identified and functionally characterized on B lymphocytes. Its critical role in T cell-dependent humoral immune responses was demonstrated by patients with the hyper-IgM syndrome, as well as by gene targeting in mice. However, in recent years it has become clear that CD40 is expressed much more broadly, including expression on monocytes, dendritic cells, endothelial cells, and epithelial cells. In addition, the CD40-ligand (CD40-L/CD154), a member of the TNF family, is also expressed more widely than activated CD4+ T cells only. Therefore it is now thought that CD40-CD40-L interactions play a more general role in immune regulation. Collectively these studies have culminated in pre-clinical and clinical studies that are in progress. This article reviews recent developments in this field of research, with main emphasis on (1) structure and expression of CD40 and its ligand; (2) CD40 signal transduction; (3) in vitro function of CD40 on different cell types; and (4) in vivo functions of CD40/CD40-L interactions.
CD40是一种细胞表面受体，属于肿瘤坏死因子受体（TNF-R）家族，最初在B淋巴细胞上被鉴定并进行功能表征。高IgM综合征患者以及小鼠基因靶向研究均证实了其在T细胞依赖性体液免疫反应中的关键作用。然而，近年来已明确CD40的表达更为广泛，包括在单核细胞、树突状细胞、内皮细胞和上皮细胞上的表达。此外，肿瘤坏死因子家族成员CD40配体（CD40-L/CD154）的表达也比仅活化的CD4 + T细胞更为广泛。因此，现在认为CD40-CD40-L相互作用在免疫调节中发挥更普遍的作用。这些研究共同促成了正在进行的临床前和临床研究。本文综述了该研究领域的最新进展，主要重点在于：（1）CD40及其配体的结构与表达；（2）CD40信号转导；（3）CD40在不同细胞类型上的体外功能；以及（4）CD40/CD40-L相互作用的体内功能。
