1. Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function
- Author
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Daniel J. Weisdorf, Michelle Pitt, Julie M. Curtsinger, Bree Foley, Sandra López-Vergès, Lewis L. Lanier, Sarah Cooley, Xianghua Luo, Michael R. Verneris, and Jeffrey S. Miller
- Subjects
Allogeneic transplantation ,medicine.medical_treatment ,Immunology ,Population ,Blotting, Western ,Cytomegalovirus ,Hematopoietic stem cell transplantation ,Biology ,Real-Time Polymerase Chain Reaction ,Virus Replication ,Biochemistry ,Cohort Studies ,Interferon-gamma ,CD57 Antigens ,NK-92 ,Receptors, KIR ,medicine ,Humans ,Transplantation, Homologous ,Interferon gamma ,RNA, Messenger ,education ,Immunobiology ,education.field_of_study ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Virology ,Transplantation ,Killer Cells, Natural ,Receptors, KIR2DL3 ,Receptors, KIR2DL2 ,Cytomegalovirus Infections ,Interleukin 12 ,NK Cell Lectin-Like Receptor Subfamily C ,Biomarkers ,medicine.drug - Abstract
During mouse cytomegalovirus (CMV) infection, a population of Ly49H+ natural killer (NK) cells expands and is responsible for disease clearance through the induction of a “memory NK-cell response.” Whether similar events occur in human CMV infection is unknown. In the present study, we characterized the kinetics of the NK-cell response to CMV reactivation in human recipients after hematopoietic cell transplantation. During acute infection, NKG2C+ NK cells expanded and were potent producers of IFNγ. NKG2C+ NK cells predominately expressed killer cell immunoglobulin–like receptor, and self-killer cell immunoglobulin–like receptors were required for robust IFNγ production. During the first year after transplantation, CMV reactivation induced a more mature phenotype characterized by an increase in CD56dim NK cells. Strikingly, increased frequencies of NKG2C+ NK cells persisted and continued to increase in recipients who reactivated CMV, whereas these cells remained at low frequency in recipients without CMV reactivation. Persisting NKG2C+ NK cells lacked NKG2A, expressed CD158b, preferentially acquired CD57, and were potent producers of IFNγ during the first year after transplantation. Recipients who reactivated CMV also expressed higher amounts of IFNγ, T-bet, and IL-15Rα mRNA transcripts. Our findings support the emerging concept that CMV-induced innate memory-cell populations may contribute to malignant disease relapse protection and infectious disease control long after transplantation.
- Published
- 2012