g-NK cells from umbilical cord blood are phenotypically and functionally different than g-NK cells from peripheral blood

Oncoimmunology. 2023 Nov 22;12(1):2283353. doi: 10.1080/2162402X.2023.2283353. eCollection 2023.

Abstract

FcRγ-deficient natural killer (NK) cells, designated as g-NK cells, exhibit enhanced antibody-dependent cellular cytotoxicity (ADCC) capacity and increased IFN-γ and TNF-α production, rendering them promising for antiviral and antitumor responses. g-NK cells from peripheral blood (PB) are often associated with prior human cytomegalovirus (HCMV) infection. However, the prevalence, phenotype, and function of g-NK cells in umbilical cord blood (UCB-g-NK) remain unclear. Here, we demonstrate significant phenotypical differences between UCB-g-NK and PB-g-NK cells. Unlike PB-g-NK cells, UCB-g-NK cells did not show heightened cytokine production upon CD16 engagement, in contrast to the conventional NK (c-NK) cell counterparts. Interestingly, following in vitro activation, UCB-g-NK cells also exhibited elevated levels of IFN-γ production, particularly when co-cultured with HCMV and plasma from g-NK+ adults. Furthermore, g-NK+ plasma from PB even facilitated the in vitro expansion of UCB-g-NK cells. These findings underscore the phenotypic and functional heterogeneity of g-NK cells based on their origin and demonstrate that components within g-NK+ plasma may directly contribute to the acquisition of an adult phenotype by the "immature" UCB-g-NK cells.

Keywords: ADCC; PB-g-NK; UCB-g-NK; g-NK+ plasma.

MeSH terms

  • Adult
  • Antibody-Dependent Cell Cytotoxicity
  • Cytomegalovirus
  • Fetal Blood*
  • Humans
  • Killer Cells, Natural
  • Lymphocyte Activation*

Grants and funding

This work was supported by INCA/DGOS PRT-K program 2021 (MV; 2021-014), the “Investissements d’avenir” Grant LabEx MAbImprove: ANR-10-LABX-53 (MV). F.G. is pursuing a joint Ph.D. program in M.V.’s lab supported by China Scholarship Council (No. 202006370198).