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

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
• g-NK⁺ plasma
• PB-g-NK
• UCB-g-NK

Acknowledgments

We express gratitude to M.L.-B. for providing the AD169 strain and to S.A. for the HFF cell line. We also acknowledge the MRI imaging facility, a member of the national infrastructure France-BioImaging supported by the French National Research Agency, for granting us access to the cytometry platform.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization M.V., T.Z.; Methodology F.G.; Data analysis and interpretation F.G.; Initial writing F.G.; Correction and samples collection M.C.M., M.C., L.C., C.M., L.V.; Reviewing & Editing M.V., T.Z.; Supervision M.V., T.Z.

Data availability statement

Corresponding authors can grant access to all study data upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2283353

Additional information

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).