Emergence of human CMV-induced NKG2C(+) NK cells is associated with CD8(+) T-cell recovery after allogeneic HCT Journal Article


Authors: van der Ploeg, K.; Sottile, R.; Kontopoulos, T.; Shaffer, B. C.; Papanicolaou, G. A.; Maloy, M. A.; Cho, C.; Robinson, K. S.; Perales, M. A.; Jean-Benoît, L. L.; Hsu, K. C.
Article Title: Emergence of human CMV-induced NKG2C(+) NK cells is associated with CD8(+) T-cell recovery after allogeneic HCT
Abstract: Cytomegalovirus (CMV) infection is associated with the expansion- of a mature NKG2C+FcεR1γ− natural killer (NK) cell population. The exact mechanism underlying the emergence of NKG2C+ NK cells, however, remains unknown. Allogeneic hematopoietic cell transplantation (HCT) provides an opportunity to longitudinally study lymphocyte recovery in the setting of CMV reactivation, particularly in patients receiving T-cell−depleted (TCD) allografts. We analyzed peripheral blood lymphocytes from 119 patients at serial time points after infusion of their TCD allograft and compared immune recovery with that in samples obtained from recipients of T-cell−replete (T-replete) (n = 96) or double umbilical cord blood (DUCB) (n = 52) allografts. NKG2C+ NK cells were detected in 92% (45 of 49) of recipients of TCD HCT who experienced CMV reactivation. Although NKG2A+ cells were routinely identifiable early after HCT, NKG2C+ NK cells were identified only after T cells could be detected. T-cell reconstitution occurred at variable times after HCT among patients and predominantly comprised CD8+ T cells. In patients with CMV reactivation, recipients of TCD HCT expressed significantly higher frequencies of NKG2C+ and CD56neg NK cells compared with patients who received T-replete HCT or DUCB transplantation. NKG2C+ NK cells after TCD HCT were CD57+FcεR1γ+ and degranulated significantly more in response to target cells compared with the adaptive the NKG2C+CD57+FcεR1γ− NK cell population. We conclude that the presence of circulating T cells is associated with the expansion of a CMV-induced NKG2C+ NK cell population, a potentially novel example of developmental cooperation between lymphocyte populations in response to viral infection. © 2023 American Society of Hematology. All rights reserved.
Keywords: adult; major clinical study; nonhuman; cd8+ t lymphocyte; cell population; allogeneic hematopoietic stem cell transplantation; natural killer cell; cytomegalovirus infection; human; male; female; article
Journal Title: Blood Advances
Volume: 7
Issue: 19
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2023-10-10
Start Page: 5784
End Page: 5799
Language: English
DOI: 10.1182/bloodadvances.2022008952
PUBMED: 37196646
PROVIDER: scopus
PMCID: PMC10561005
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Katharine C. Hsu -- Source: Scopus
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MSK Authors
  1. Miguel-Angel Perales
    913 Perales
  2. Katharine C Hsu
    184 Hsu
  3. Molly Anna Maloy
    269 Maloy
  4. Christina Cho
    134 Cho
  5. Brian Carl Shaffer
    164 Shaffer