title: Characterization of IFNγ-producing natural killer cells induced by cytomegalovirus reactivation after haploidentical hematopoietic stem cell transplantation.
abstract: During human cytomegalovirus (CMV) infection after umbilical cord blood or HLA-matched hematopoietic stem cell transplantation (HSCT), a population of NKG2C-expressing natural killer (NK) cells expand and persist. The expanded NK cells express high levels of inhibitory killer immunoglobulin-like receptors (KIR) specific for self-HLA and potently produce IFNγ. However, it remains unknown whether similar events would occur after haploidentical HSCT (haplo-HSCT). Here, we demonstrated that IFNγ-producing NK cells were expanded in haplo-HSCT patients with CMV reactivation. We then identified these expanded cells as a subset of CD56dim NK cells that expressed higher levels of both NKG2C and KIR, but lower level of NKG2A. Functionally, the subset of NK cells expressing NKG2C and self-KIR in patients with CMV reactivation accounted for IFNγ production in response to K562 cells. However, these phenomena were not observed in patients without CMV reactivation. We therefore characterized a subset of NK cells with the CD56dim, NKG2C+, and self-KIR+ phenotype that expanded and were responsible for IFNγ production during CMV infection after haplo-HSCT. Together, these findings support a notion that CMV reactivation induces expansion of more mature NK cells with memory-like features, which contributes to long-term control of both CMV infection and leukemia relapse after haplo-HSCT.
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Sujun
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Hematology, Air Force General Hospital, the Chinese People's Liberation Army, Beijing, China.
authors.forename: Hengxiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Hematology, Air Force General Hospital, the Chinese People's Liberation Army, Beijing, China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Yan
authors.affiliation: Institute of Translational Medicine, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Guo
authors.affiliation: Institute of Translational Medicine, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Institute of Translational Medicine, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Hematology, Air Force General Hospital, the Chinese People's Liberation Army, Beijing, China.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, Air Force General Hospital, the Chinese People's Liberation Army, Beijing, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yangzhi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hematology, Air Force General Hospital, the Chinese People's Liberation Army, Beijing, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yehui
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.|Institute of Translational Medicine, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous; D014775:Virus Activation / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D055654:NK Cell Lectin-Like Receptor Subfamily C; D024661:Potassium Channels, Inwardly Rectifying; D007371:Interferon-gamma
keywords: IFNγ; KIR; NK cells; NKG2C; Pathology Section; cytomegalovirus