马立克氏病强弱毒株感染鸡在免疫检查点分子差异及机制

马立克氏病是由马立克氏病病毒（MDV）引起的肿瘤性疾病，也是国际上第一个能用疫苗进行有效预防的肿瘤性传染病。虽然MDV的致病机理研究较多，但免疫机理研究很少。本项目将在前期发现增强机体天然免疫有助于抑制MDV致病的基础上，利用流式细胞仪分选技术，结合特异性分子靶标，通过比较疫苗毒如CVI988和强毒RB1B感染鸡在免疫检查点分子上的差异，发现疫苗免疫调节机制，特别是在弱毒与强毒同时存在的情况下，疫苗如何调节机体的免疫功能去清除强毒感染产生的转化癌细胞，明确PD-1和CTLA-4标志物在MDV肿瘤形成中的作用，寻找和发现新的免疫检查点分子，确定参与免疫调节的主要T细胞，阐明MDV疫苗毒感染鸡的免疫调节机制，不仅为疫苗提高免疫效力，更为比较生物学和人类癌症的预防提供新思路。

Marek’s disease (MD), caused by Marek’s disease virus (MDV), is a commercially important neoplastic disease of poultry, which is the first cancer controlled by mass vaccination in the world. There were only few reports about the immune mechanism of vaccine although much more papers on the pathogenesis of MDV. Based on our pre-research results that increasing the native immunity will be helpful to inhibit the pathogenosis of MDV, for this project we will compare the molecular difference at the immune checkpoint in the T cells in chickens infected with virulent or avirulent MDV by flowcytometer and molecular targets. We will investigate the mechanism of vaccination, especially how the vaccine function to regulate the immune system to kill the new tumor cells transformed by virulent MDV. Also we will investigate the function of PD-1 and CTLA-4 in the MDV tumor development and find the new potential molecule of the immune checkpoints. Our results will help us not only to understand the function of mainly regulate cells in MD control and improve the effect of vaccination but also to give us some new clues to prevent human cancer in the comparative biomedicine.