Basic research of defining the function of CD26 on human immune system and its clinical application for autoimmune diseases.

CD26是一种110 KDa的表面糖蛋白，具有DPPIV酶活性，具有多种生物学功能。与CD28共刺激相比，CD26共刺激可诱导CD4T细胞产生IL-10和表达CTLA-4，提示CD26协同刺激具有负激活途径。我们还发现CD2 6(高)CD8T细胞属于早期效应记忆T细胞亚群，与CD2 8介导的共刺激相比，CD2 6介导的共刺激CD8+T细胞优先通过Grazyme B、肿瘤坏死因子α和Fas配体发挥细胞毒作用。此外，我们还发现CD26+T细胞在人淋巴细胞介导的GVHD中起着重要作用，抗CD26单抗是治疗HU-PBL-NOG小鼠GVHD的有效方法。此外，我们发现CD26/DPPIV的基因或药物抑制在体外和体内都能促进内皮细胞的生长，提示DPPIV抑制在内皮细胞生长中起关键作用，并可能在糖尿病血管并发症后局部循环的恢复中发挥潜在作用。我们的结果有力地表明，CD26/DPPIV是治疗特定免疫疾病的合适靶点。

CD26 is a 110-KDa surface glycoprotein with DPPIV enzyme activity that has many biological functions. We showed that CD26 costimulation induced IL -10 production and CTLA-4 expression in CD4 T cells compared to CD28 costimulation suggesting that CD26 coslimulation has a negative activation pathway. We also showed that CD26 (high) CD8 T cells belong to the early effector memory T-cell subset and that CD26 mediated co-stimulation of CD8+T cells exerts a cytotoxic effect preferentially via gramzyme B, TNF-α and Fas-ligand compared to that obtained through CD28-mediated costimulation. Moreover, we showed that CD26+T cells play an important role in GVHD mediated by human lymphocytes, and that anti-CD26mAb is an effective treatment for GVHD in hu-PBL-NOG mouse model. In addition we found that genetical or pharmacological inhibition of CD26/DPPIV enhances endothelial growth both in vitro and in vivo, suggesting that DPPIV inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications. Our results strongly suggest that CD26/DPPIV is an appropriate therapeutic target for the treatment of selected immune disorders.