The newborn human NK cell repertoire is phenotypically formed but functionally reduced.

ABSTRACT

BACKGROUND: Infection is a leading cause of death worldwide in babies under 1 month of age. Better vaccines and therapeutics are desperately needed for this vulnerable population. METHODS: Because newborns rely heavily on the innate immune system, we evaluated cell phenotype and function of some of the earliest cellular responders during infection, natural killer (NK) cells. We used mass cytometry to provide a comprehensive comparison of NK cells from umbilical cord blood and adult peripheral blood. RESULTS: In unsupervised analyses, including viSNE and principal component analysis, the structure of the cord blood and adult NK cell repertoires are highly similar, distinguishable mainly by maturity-related markers expressed on rare subpopulations of cells. However, in functional analyses, cord blood NK cells show reduced degranulation and cytokine production following target recognition, as well as antibody-dependent cell-mediated cytotoxicity and apoptosis induction in targets. CONCLUSIONS: These findings show that the structure of the NK cell repertoire is intact at birth, suggesting great potential for vaccine and therapeutic strategies targeting this cell population. © 2016 International Clinical Cytometry Society.