协同刺激因子B7家族成员的抑制性受体与负向免疫调节

Inhibitory Receptors for the Molecules of B7 Family and the Negative Immune Regulation

维持淋巴细胞的正常功能需要正负向协同刺激信号的同时参与。两种信号决定了T、B细胞对抗原特异性刺激的敏感性和应答方式。二者的平衡使机体在避免对自身抗原产生不适当反应的同时,又能对外来抗原显示足够强的应答能力。多年来有关协同信号的研究,对相关分子结构和功能的认识已大大深化,特别是其中的B7分子及其受体家族。该家族的负向调控作用是通过其抑制性受体来实现的。目前已发现3种抑制性受体:细胞毒性T细胞相关分子(CTLA-4)、程序性死亡分子(PD-1)和B、T细胞弱化因子(BTLA)。对其效应机制的研究,将对免疫调节以及自身免疫、肿瘤免疫和移植免疫产生深远影响。

Maintenance of lymphocyte homeostasis is regulated by a number of positive and negative costimulatory signals, which determine the thresholds for antigen-specific stimulation of T and B cells. The balance between two kinds of signals ensures an effective response to foreign antigens for host protection, while avoiding inappropriate reaction to self antigens. Intensive investigations on the structure and function of the costimulation- related molecules revealed that important roles are played by the members of B7 family. The negative control activity exerted by the family is tightly dependent on the inhibitory receptors. Three kinds of B7-ligating receptors with down regulatory activity have been identified, including CTLA-4, PD-1 and BTLA. Studies on the inhibitory recep- tors have provided a better understanding of the mechanisms for immune regulation, which would help to lay a basis for therapeutic applications to human diseases like cancers, autoimmune disorders and transplantation rejection.