JCI Insight (Feb 2022)

Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation

  • Xing-Xing Yu,
  • Qian-Nan Shang,
  • Xue-Fei Liu,
  • Mei He,
  • Xu-Ying Pei,
  • Xiao-Dong Mo,
  • Meng Lv,
  • Ting-Ting Han,
  • Ming-Rui Huo,
  • Xiao-Su Zhao,
  • Ying-Jun Chang,
  • Yu Wang,
  • Xiao-Hui Zhang,
  • Lan-Ping Xu,
  • Kai-Yan Liu,
  • Xiang-Yu Zhao,
  • Xiao-Jun Huang

Journal volume & issue
Vol. 7, no. 3

Abstract

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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.

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