Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation.
Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation.
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供体 NKG2C 纯合性有助于半相合移植后 CMV 清除。
DOI：
10.1172/jci.insight.149120
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发表时间：
2022-02-08
期刊：
影响因子：
8
通讯作者：
Huang XJ
中科院分区：
文献类型：
--
作者：
Yu XX;Shang QN;Liu XF;He M;Pei XY;Mo XD;Lv M;Han TT;Huo MR;Zhao XS;Chang YJ;Wang Y;Zhang XH;Xu LP;Liu KY;Zhao XY;Huang XJ
巨细胞病毒感染仍然是异基因造血干细胞移植（allo-HSCT）后发病和死亡的重要原因。几位研究者报告称，适应性NKG 2C + NK细胞在CMV再激活期间持续扩增。在我们的研究中，入组了2个队列，以探索NKG 2C基因型、NKG 2C + NK细胞重建和CMV感染之间的关系。多因素分析显示，供体NKG 2C基因缺失是CMV再激活和难治性CMV再激活的独立预后因素。此外，移植后接受NKG 2Cwt/del供体细胞移植的患者中，适应性NKG 2C + NK细胞的定量和定性重建沿着抗CMV功能显著低于接受NKG 2Cwt/wt供体细胞移植的患者。移植后第30天，治疗难治性CMV再激活患者的NKG 2C + NK细胞定量重建显著低于无CMV再激活和非难治性CMV再激活患者。在人源化CMV感染的小鼠中，我们发现，与来自NKG 2Cwt/del供体的那些相比，来自NKG 2Cwt/wt供体的适应性NKG 2C + NK细胞诱导NKG 2C + NK细胞更早和更强的扩增以及体内更早和更强的CMV清除。总之，供体NKG 2C纯合性通过促进单倍体相合allo-HSCT后适应性NKG 2C + NK细胞的定量和定性重建而有助于CMV清除。
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.