Denton M D, Reul R M, Dharnidharka V R, Fang J C, Ganz P, Briscoe D M
Department of Pediatrics, Children's Hospital, Boston, Massachusetts 02115, USA.
Pediatr Transplant. 1998 Feb;2(1):6-15.
Major advances have been made in understanding the expression and function of CD40 and its ligand CD154. It is now clear that CD40/CD154 interactions are critical in many aspects of the immune response, including T cell activation, T cell-dependent macrophage activation, T cell-B cell interactions and endothelial activation. Moreover, increasing evidence supports a central role for CD40/CD154 interactions in the immune processes of allograft rejection. Functional studies using blocking monoclonal antibodies have revealed beneficial effects of interupting CD40/CD154 co-stimulation in animal models of transplantation, particularly in association with interuption of the CD28/B7 pathway. A next step is to develop new therapeutic approaches to interrupting this pathway in humans, either through the development of receptor antagonists or through the understanding of intracellular signaling pathways utilized by these molecules.
在理解CD40及其配体CD154的表达和功能方面已取得重大进展。现在很清楚，CD40/CD154相互作用在免疫反应的许多方面都至关重要，包括T细胞活化、T细胞依赖性巨噬细胞活化、T细胞与B细胞的相互作用以及内皮细胞活化。此外，越来越多的证据支持CD40/CD154相互作用在同种异体移植排斥反应的免疫过程中起核心作用。使用阻断性单克隆抗体的功能研究表明，在移植动物模型中阻断CD40/CD154共刺激具有有益效果，特别是与阻断CD28/B7途径相关联时。下一步是开发新的治疗方法，通过开发受体拮抗剂或通过了解这些分子所利用的细胞内信号通路来在人类中阻断这一途径。
