造血干细胞移植后巨细胞病毒（CMV）再活化率高，增加移植相关死亡风险。适应性NKG2C+NK细胞在体内CMV再活化时可以迅速扩增，可控制CMV再活化；但目前调控移植后NKG2C+NK细胞重建机制不清。我们前期发现，移植后NK细胞功能快速重建与CMV再活化率降低相关。本研究旨在以移植后NKG2C+NK细胞重建为主线，借助临床队列、转录组学、全基因组甲基化测序及动物模型，探讨供者NKG2C基因型对移植后NKG2C+NK细胞重建调控及对CMV再活化影响；找到与NKG2C基因型相关的NKG2C+NK细胞早期快速重建的关键通路；建立体外培养体系，实现NKG2C+NK细胞的快速扩增，借助人源化CMV小鼠模型，证实过继性回输NKG2C+NK细胞可促进NK重建并降低移植后CMV再活化；从而阐明移植后调控NKG2C+NK细胞重建的机制，降低CMV再活化的风险，为建立促进移植后NK细胞重建新方法奠定基础。

Cytomegalovirus (CMV) reactivation increases the risk of transplant-related mortality post hematopoietic stem cell transplantation. Adaptive NKG2C+ NK cells can rapidly proliferate when in vivo CMV reactivation and control CMV reactivation; however, the mechanisms of regulating NKG2C+ NK cell reconstitution after transplantation are unclear. We found earlier that the rapid reconstitution of NK cell function after transplantation was associated with a decreased CMV reactivation post transplantation. Based on clinical cohort study, single cell sequencing and animal models, the aims of this study are to investigate the effect of donor NKG2C genotypes on NKG2C+ NK cell reconstitution and CMV reactivation after transplantation, to find the key pathways regulating donor NKG2C genotype-related NKG2C+ NK cells’ rapid reconstitution. Guided with the molecular pathways regulating donor NKG2C genotype-related NKG2C+ NK cells’ rapid reconstitution, we could build in vitro culture system to achieve rapid expansion of NKG2C+ NK cells. Finally, using the humanized CMV mouse model, we want to confirm the adoptive transfer of expanded NKG2C+ NK cells can promote the NK cells reconstitution and reduce the CMV reactivation after transplantation. Thus, the mechanism of NKG2C+ NK cell reconstitution after transplantation is clarified and the risk of CMV reactivation is reduced, laying a theoretical foundation for establishing a new method to promote NK cell reconstitution and guiding donor selection.