The Emory Transplant Center and the Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Curr Opin Organ Transplant. 2008 Aug;13(4):366-72. doi: 10.1097/MOT.0b013e328306115b.
The manipulation of costimulatory pathways holds tremendous potential for treating immunologically mediated diseases. In this article, we review the role of molecules that deliver a positive second signal that, together with an antigen-specific signal from the T-cell receptor, is necessary to promote complete T-cell activation, differentiation and development of effector function.
Numerous positive costimulatory molecules have been identified: CD28/B7, induced costimulatory/induced costimulatory ligand, CD40/CD154, OX40/OX40L, CD27/CD70, 4-1BB/4-1BBL, LIGHT/herpes virus entry mediator, glucosyltransferase R and T-cell immunoglobulin mucin molecules. Many of these have been only recently discovered and remain incompletely studied. Recent work has demonstrated that some costimulatory molecules bind ligands expressed by nonprofessional activated protein C, some modulate regulatory T cells and some sustain rather than initiate immune responses. Emerging data suggest that the costimulatory pathways are redundant and that the various costimulatory molecules affect different T-cell populations and act at different times during the course of the immune response.
These observations suggest that the therapeutic exploitation of strategies targeting costimulatory molecules will require carefully timed interventions directed against multiple pathways.
目的综述：共刺激途径的调控在治疗免疫介导性疾病方面具有巨大的潜力。本文综述了传递正向第二信号的分子的作用，该信号与 T 细胞受体的抗原特异性信号一起，是促进完全 T 细胞激活、分化和效应功能发展所必需的。
最近的发现：已鉴定出许多正向共刺激分子：CD28/B7、诱导共刺激/诱导共刺激配体、CD40/CD154、OX40/OX40L、CD27/CD70、4-1BB/4-1BBL、LIGHT/疱疹病毒进入介体、葡萄糖基转移酶 R 和 T 细胞免疫球蛋白黏蛋白分子。其中许多是最近才发现的，仍未得到充分研究。最近的研究表明，一些共刺激分子结合非专业激活蛋白 C 表达的配体，一些调节调节性 T 细胞，一些维持而不是启动免疫反应。新出现的数据表明，共刺激途径是冗余的，各种共刺激分子影响不同的 T 细胞群体，并在免疫反应过程中的不同时间发挥作用。
总结：这些观察结果表明，针对共刺激分子的治疗性开发策略将需要针对多个途径进行精心设计的干预。
