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. 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. 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.
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 al 12 and A. These 2 subsets differ in proliferative potential, cytolytic activity, and capability of secreting IFN-γ or TNF-α upon cytokine stimulation. Different experimental evidence supports the notion that peripheral blood CD56 bright give rise to CD56 dim NK cells. Model of human CD56 dim NK-cell differentiation. CD57 expression is acquired at later stages and marks terminally differentiated cells with high cytolytic activity but very low proliferative potential. 10 These data support the notion that, in vivo, human CD56 bright NK cells may undergo progressive differentiation ending with a CD94 lowCD62L negCD56 dim phenotype. 9 In agreement with these concepts, recent studies revealed that the density of surface expression of CD94 or of CD62L identifies functional intermediaries between CD56 bright and CD56 dim human NK-cell subsets. 7-9 In addition, they have longer telomeres than CD56 dim cells. 6, 7 In turn, CD56 bright PB NK cells are thought to give rise to CD56 dim cells because they appear first after HSC transplantation and in cytokine-driven models of NK-cell in vitro differentiation.
CD56 bright cells have been shown to derive from CD34 + hemopoietic stem cells (HSC) via phenotypically identified stages.
Human mature natural killer (NK) cells are generally divided into 2 subsets based on the relative surface density of CD56 antigen: CD56 bright cells, predominant in secondary lymphoid tissues, and CD56 dim cells, predominant in peripheral blood (PB).
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