Oncotarget

Research Papers: Pathology:

Characterization of IFNγ-producing natural killer cells induced by cytomegalovirus reactivation after haploidentical hematopoietic stem cell transplantation

Fengyan Jin, Hai Lin, Sujun Gao, Hengxiang Wang, Hongmin Yan, Jinglong Guo, Zheng Hu, Chunhui Jin, Yongqi Wang, Zhidong Wang, Yangzhi Zhao, Yu Liu, Xiaoli Zheng, Yehui Tan, Wei Li, Yun Dai and Yanping Yang _

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Oncotarget. 2017; 8:51-63. https://doi.org/10.18632/oncotarget.13916

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Abstract

Fengyan Jin1, Hai Lin1, Sujun Gao1, Hengxiang Wang2, Hongmin Yan2, Jinglong Guo3, Zheng Hu3, Chunhui Jin3, Yongqi Wang2, Zhidong Wang2, Yangzhi Zhao1, Yu Liu1, Xiaoli Zheng2, Yehui Tan1, Wei Li1, Yun Dai1,3 and Yanping Yang1

1 Department of Hematology, Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, China

2 Department of Hematology, Air Force General Hospital, the Chinese People’s Liberation Army, Beijing, China

3 Institute of Translational Medicine, the First Bethune Hospital of Jilin University, Changchun, Jilin, China

Correspondence to:

Yun Dai, email:

Yanping Yang, email:

Keywords: NK cells, NKG2C, KIR, IFNγ, cytomegalovirus, Pathology Section

Received: April 11, 2015 Accepted: December 02, 2016 Published: December 12, 2016

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.


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