Natural Killer Cell Development and Maturation Revisited: Possible Implications of a Novel Distinct Lin - CD34 + DNAM-1 bright CXCR4 + Cell Progenitor.

Since the first description of natural killer (NK) cells, the view on their role in innate immunity has evolved considerably. In addition to first-line defense against transformed and pathogen-infected autologous cells, NK cells contribute to modulate adaptive immune responses and in some cases acquire specialized functions, including exhausted, adaptive, and decidual NK cells. NK cells derive from CD34 ⁺ progenitors, in vivo and in vitro ; however, it is unclear whether the high phenotype diversity in vivo may be generated from these precursors alone. The recent characterization of a novel CD34 ⁺ DNAM-1 ^bright CXCR4 ⁺ precursor giving rise to apparently licensed and functional maturing NK cells may suggest the possibility for a higher than expected common lymphocyte precursor diversity and a consequently higher peripheral NK cell phenotype variability. Here, we review the evidences on NK cell central and peripheral development from CD34 ⁺ precursors and propose a possible updated reading frame based on the characterization of CD34 ⁺ DNAM-1 ^bright CXCR4 ⁺ cell progenies, which favors the possibility of concurrent NK cell maturation from different CD34 ⁺ precursors.