The biology of human natural killer-cell subsets

Human natural killer (NK) cells comprise ≈15% of all circulating lymphocytes. Owing to their early production of cytokines and chemokines, and ability to lyse target cells without prior sensitization, NK cells are crucial components of the innate immune system. Human NK cells can be divided into two subsets based on their cell-surface density of CD56 – CD56bright and CD56dim – each with distinct phenotypic properties. Now, there is ample evidence to suggest that these NK-cell subsets have unique functional attributes and, therefore, distinct roles in the human immune response. The CD56dim NK-cell subset is more naturally cytotoxic and expresses higher levels of Ig-like NK receptors and FCγ receptor III (CD16) than the CD56bright NK-cell subset. By contrast, the CD56bright subset has the capacity to produce abundant cytokines following activation of monocytes, but has low natural cytotoxicity and is CD16dim or CD16−. In addition, we will discuss other cell-surface receptors expressed differentially by human NK-cell subsets and the distinct functional properties of these subsets.