Tsushima Fumihiko, Iwai Hideyuki, Otsuki Noriko, Abe Masaaki, Hirose Sachiko, Yamazaki Tomohide, Akiba Hisaya, Yagita Hideo, Takahashi Yuzo, Omura Ken, Okumura Ko, Azuma Miyuki
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Eur J Immunol. 2003 Oct;33(10):2773-82. doi: 10.1002/eji.200324084.
Programmed death-1 (PD-1) and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that may be involved in the regulation of immune responses. We examined the roles of these molecules in mouse hapten-induced contact hypersensitivity (CH). Administration of anti-PD-1 mAb at sensitization significantly enhanced and prolonged ear swelling. Treatment with anti-B7-H1 mAb, but not anti-B7-DC mAb, also enhanced CH reactions. The anti-PD-1 mAb treatment at sensitization significantly increased the T cell number of draining lymph nodes (DLN). B7-H1 was induced on activated T cells and antigen-presenting cells (APC) in the skin and the DLN, whereas B7-DC expression was restricted to dendritic cells (DC) in the dermis and the DLN. A particular subset of DC, B7-H1(+)B7-DC(-)CD86(low), was found in sensitized DLN. The blockade of B7-H1, but not B7-DC, dramatically enhanced the initial T cell proliferative responses against hapten-pulsed DLN APC, suggesting the preferential contribution of B7-H1 to the T cell-APC interaction. Our results demonstrate the regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. The PD-1-B7-H1 pathway may play a unique role in regulating inflammatory responses.
程序性死亡因子1（PD-1）及其配体B7-H1/PD-L1和B7-DC/PD-L2是CD28-B7家族的新成员，可能参与免疫反应的调节。我们研究了这些分子在小鼠半抗原诱导的接触性超敏反应（CH）中的作用。致敏时给予抗PD-1单克隆抗体可显著增强并延长耳部肿胀反应。用抗B7-H1单克隆抗体治疗可增强CH反应，而抗B7-DC单克隆抗体则无此作用。致敏时用抗PD-1单克隆抗体治疗可显著增加引流淋巴结（DLN）中的T细胞数量。B7-H1在皮肤和DLN中活化的T细胞及抗原呈递细胞（APC）上被诱导表达，而B7-DC的表达则局限于真皮和DLN中的树突状细胞（DC）。在致敏的DLN中发现了一个特殊的DC亚群，即B7-H1(+)B7-DC(-)CD86(low)亚群。阻断B7-H1而非B7-DC可显著增强针对半抗原刺激的DLN APC的初始T细胞增殖反应，提示B7-H1在T细胞与APC相互作用中起优先作用。我们的结果证明了PD-1在半抗原诱导免疫反应中的调节作用以及B7-H1和B7-DC的不同作用。PD-1-B7-H1通路可能在调节炎症反应中发挥独特作用。
