Purpose of review: Human natural killer cell deficiencies are a relevant clinical entity that provides insight into the role of natural killer cells in host defense, as well as the basic biology of natural killer cells. Since previously reviewing these disorders, significant developments warrant their reconsideration.
Recent findings: Human natural killer cell deficiencies can occur as part of a more pervasive immunodeficiency syndrome or, rarely, in isolation. The most informative examples of the former are in the context of a known genetic defect, because the deficiency of natural killer cell development or activity can be attributed to the specific gene function. Since last reviewed, there are five human gene mutations that are now appreciated to affect natural killer cells, and additional new insights into natural killer cell biology have been obtained through seven others. Six new reports of isolated natural killer cell deficiencies, as well as a suggested classification scheme, are also reviewed.
Summary: Appreciation of human genetic syndromes that include natural killer cell deficiencies, as well as new cases of isolated natural killer cell deficiencies, continue to advance the understanding of natural killer cell biology and solidify the role of natural killer cells in defense against human herpesviral infection.