细胞因子基因多态性与T细胞在allo-HSCT后EBV再激活及相关疾病中的作用和机制研究

病毒感染是制约异基因造血干细胞移植（allo-HSCT）预后的重要并发症之一。allo-HSCT后EBV再激活可引起包括致死性的移植后淋巴细胞增殖性疾病在内的EBV相关疾病。申请人及团队的前期研究发现：移植后EBV再激活和相关疾病发病率存在地区差异，其易感性与细胞因子基因多态性存在关联，但机理尚不清楚。慢性病毒感染患者存在T细胞耗竭，其机制之一是细胞因子影响共抑制信号分子表达和通路激活。本项目拟通过临床病例、体外实验和动物模型研究细胞因子基因多态性与allo-HSCT后EBV再激活、相关疾病发生发展及T细胞耗竭的关联及机理，最终阐明基因多态性影响allo-HSCT后EBV相关疾病的机理。

Viral Infections are important complications after allogeneic stem cell transplantation (allo-HSCT) which influences the prognosis. EBV reactivation after allo-HSCT can cause a spectrum of EBV associated diseases including post-transplant lymphoproliferative disease which is life-threatening. Our previous studies demonstrated that the incidence of EBV reactivation and associated diseases were different among regions and associated with cytokine gene polymorphism. However, the mechanism remains unclear. T cell exhaustion has been observed in chronic viral infection. Previous studies indicated that cytokine could influence the expression of co-inhibitory receptors and pathway activation, and, therefore influence T cell exhaustion. Here, the association between cytokine gene polymorphism and T cell exhaustion as well as EBV reactivation/ associated diseases after allo-HSCT will be explored in patients, in vitro and humanized mouse models to illuminate the mechanism of the development of EBV diseases after allo-HSCT in respect to cytokine gene polymorphism.