Human natural killer (NK) cell formation is poorly known; nevertheless, instances of human primary immunodeficiency that influence the production of mature human NK cell subsets provide crucial insights. Monogenic primary immunodeficiencies that highlight key needs for human NK cell development are reviewed in this study. Increased sensitivity in NK cell phenotyping has identified NK cell defects that influence the distribution of NK cell subsets in peripheral blood. These, in addition to those that inhibit the formation of mature NK cells, reveal critical needs for human NK cell maturation and homeostasis. The severe and frequently life-threatening viral vulnerability that these are associated with emphasizes the nonredundant function that NK cells play in human health and illness.

Human NK cell deficiency can develop when NK cells are present in normal numbers but only certain subsets are impaired.