Identification of a novel cord blood NK cell subpopulation expressing functional programmed death receptor-1

• Published in: Frontiers in immunology Vol. 14; p. 1183215
• Main Authors: Greppi, Marco, Obino, Valentina, Goda, Rayan, Rebaudi, Federico, Carlomagno, Simona, Della Chiesa, Mariella, Sivori, Simona, Ubezio, Gianluca, Agostini, Vanessa, Bo, Alessandra, Pesce, Silvia, Marcenaro, Emanuela
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22-06-2023
• Subjects: Adult; cord blood (CB); Cytomegalovirus Infections - metabolism; Fetal Blood; human natural killer (NK) cells; Humans; Immunology; Infant, Newborn; Killer Cells, Natural - metabolism; killer ig-like receptor (KIR); NK cell maturation; NKG2A; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; programmed death receptor 1 (PD-1); Receptors, Death Domain - metabolism; human natural killer (NK) cells; programmed death receptor 1 (PD-1); NK cell maturation; killer ig-like receptor (KIR); NKG2A; immune checkpoint; human cytomegalovirus (CMV); cord blood (CB)
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1183215

Natural Killer cells (NKs) represent the innate counterpart of TCRαβ lymphocytes and are characterized by a high anti-tumor and an anti-viral cytotoxic activity. Recently, it has been demonstrated that NKs can express PD-1 as an additional inhibitory receptor. Specifically, PD-1 was identified on a subpopulation of terminally differentiated NKs from healthy adults with previous HCMV infection. So far it is unknown whether PD-1 appears during NK-cell development and whether this process is directly or indirectly related to HCMV infection.
In this study, we analyzed the expression and function of PD-1 on Cord Blood derived NKs (CB-NKs) on a large cohort of newborns through multiparametric cytofluorimetric analysis.
We identified PD-1 on CB-NKs in more than of half the newborns analyzed. PD-1 was present on CD56
NKs, and particularly abundant on CD56
NKs, but only rarely present on CD56
NKs. Importantly, unlike in adult healthy donors, in CB-NKs PD-1 is co-expressed not only with KIR, but also with NKG2A. PD-1 expression was independent of HCMV mother seropositivity and occurs in the absence of HCMV infection/reactivation during pregnancy. Notably, PD-1 expressed on CB-NKs was functional and mediated negative signals when triggered.
To our understanding, this study is the first to report PD-1 expression on CB derived NKs and its features in perinatal conditions. These data may prove important in selecting the most suitable CB derived NK cell population for the development of different immunotherapeutic treatments.