Model of human CD56^dim NK-cell differentiation. Different experimental evidence supports the notion that peripheral blood CD56^bright give rise to CD56^dim NK cells. These 2 subsets differ in proliferative potential, cytolytic activity, and capability of secreting IFN-γ or TNF-α upon cytokine stimulation. With respect to cytokine secretion, however, recent studies revealed that CD56^dim are capable of rapid secretion upon cell triggering via activating receptors (Fauriat et al¹²  and A. De Maria et al, personal communication). Two independent articles showed that CD56^dim cells can be further fractionated into different cell subsets on the basis of their surface markers and function. As depicted in this schematic figure, the progression of CD56^dim toward putative terminally differentiated NK cells is accompanied by the progressive loss of their proliferative capacity and the acquisition of more efficient cytolytic activity. Different maturational stages can be identified on the basis of the progressive down-regulation of CD94 and the expression of (1or more) KIRs and of CD16. CD57 expression is acquired at later stages and marks terminally differentiated cells with high cytolytic activity but very low proliferative potential.