| Title | Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation |
| Authors | Yu, Xing-Xing Shang, Qian-Nan Liu, Xue-Fei He, Mei Pei, Xu-Ying Mo, Xiao-Dong Lv, Meng Han, Ting-Ting Huo, Ming-Rui Zhao, Xiao-Su Chang, Ying-Jun Wang, Yu Zhang, Xiao-Hui Xu, Lan-Ping Liu, Kai-Yan Zhao, Xiang-Yu Huang, Xiao-Jun |
| Affiliation | Peking Univ, Peking Univ Peoples Hosp, Natl Clin Res Ctr Hematol Dis,Inst Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, Beijing, Peoples R China Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China Beijing Engn Lab Cellular Therapy, Beijing, Peoples R China |
| Keywords | HUMAN CYTOMEGALOVIRUS-INFECTION NATURAL-KILLER-CELLS COPY-NUMBER RISK-FACTOR NK CELLS REACTIVATION LEUKEMIA DELETION RECEPTOR DISEASE |
| Issue Date | 8-Feb-2022 |
| Publisher | JCI INSIGHT |
| Abstract | CMV infection remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several investigators have reported that adaptive NKG2C+ NK cells persistently expand during CMV reactivation. In our study, 2 cohorts were enrolled to explore the relationships among the NKG2C genotype, NKG2C+ NK cell reconstitution, and CMV infection. Multivariate analysis showed that donor NKG2C gene deletion was an independent prognostic factor for CMV reactivation and refractory CMV reactivation. Furthermore, adaptive NKG2C+ NK cells' quantitative and qualitative reconstitution, along with their anti-CMV function after transplantation, was significantly lower in patients grafted with NKG2Cwt/del donor cells than in those grafted with NKG2Cwt/wt donor cells. At day 30 after transplantation, quantitative reconstitution of NKG2C+ NK cells was significantly lower in patients with treatment-refractory CMV reactivation than in patients without CMV reactivation and those with nonrefractory CMV reactivation. In humanized CMV-infected mice, we found that, compared with those from NKG2Cwt/del donors, adaptive NKG2C+ NK cells from NKG2Cwt/wt donors induced earlier and stronger expansion of NKG2C+ NK cells as well as earlier and stronger CMV clearance in vivo. In conclusion, donor NKG2C homozygosity contributes to CMV clearance by promoting the quantitative and qualitative reconstruction of adaptive NKG2C+ NK cells after haploidentical allo-HSCT. |
| URI | http://hdl.handle.net/20.500.11897/637987 |
| DOI | 10.1172/jci.insight.149120 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
