Journal
ONCOTARGET
Volume 8, Issue 1, Pages 51-63Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13916
Keywords
NK cells; NKG2C; KIR; IFN gamma; cytomegalovirus; Pathology Section
Categories
Funding
- Norman Bethune Program of Jilin University [2012224]
- National Natural Science Foundation of China [81100350, 81471165, 81670190]
- Fundamental Research Fund of the Jilin University [450060445226]
- Science Foundation for the 49th Chinese Postdoc Grant [20110490155]
- Jilin Province health family planning research plan [20142041]
- Jilin Province young Science Foundation of technology development plan [201201019]
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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 IFN gamma. However, it remains unknown whether similar events would occur after haploidentical HSCT (haplo-HSCT). Here, we demonstrated that IFN gamma-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 IFN. 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 IFN gamma 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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