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

CD 26是一种分子量为110-KDa的表面糖蛋白，具有DPPIV酶活性，具有多种生物学功能。我们发现，与CD 28共刺激相比，CD 26共刺激诱导CD 4 T细胞中IL-10的产生和CTLA-4的表达，表明CD 26共刺激具有负活化途径。我们还发现，CD 26（高）CD 8 T细胞属于早期效应记忆T细胞亚群，并且与通过CD 28介导的共刺激获得的细胞毒性效应相比，CD 26介导的CD 8 +T细胞的共刺激优先通过gramzyme B、TNF-α和Fas-配体发挥细胞毒性效应。此外，我们发现，CD 26 +T细胞在人淋巴细胞介导的GVHD中起重要作用，并且抗CD 26 mAb是hu-PBL-NOG小鼠模型中GVHD的有效治疗。此外，我们发现，在体外和体内，CD 26/DPPIV的遗传或药理学抑制增强内皮生长，这表明DPPIV抑制在内皮生长中起着关键作用，并可能在糖尿病血管并发症后局部循环的恢复中起着潜在的作用。我们的研究结果强烈表明，CD 26/DPPIV是一个合适的治疗目标，用于治疗选定的免疫疾病。

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.