Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation.
JCI Insight
; 7(3)2022 02 08.
Article
em En
| MEDLINE
| ID: mdl-34990406
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doadores de Tecidos
/
Células Matadoras Naturais
/
Infecções por Citomegalovirus
/
Transplante de Células-Tronco Hematopoéticas
/
Subfamília C de Receptores Semelhantes a Lectina de Células NK
/
Rejeição de Enxerto
/
Mutação
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Qualitative_research
Limite:
Adolescent
/
Adult
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China