Cyclophosphamide in aplastic anemia?

stances, future investigations will help clarify the division of labor among NK-cell subsets. Although further studies are necessary to more fully understand NK-cell responses to target cell recognition, the work by Fauriat et al sheds light on the functional heterogeneity of human CD56bright and CD56dim NK-cell subsets. This study also advances our knowledge on how multiple NK cell–activating receptors contribute to cytokine and chemokine production of CD56dim NK cells upon target cell recognition. The authors show that CD56dim NK cells produce IFN, rather than CD56bright NK cells, upon target cell recognition. Interestingly, less than 10% of CD56dim NK cells are IFN–producing cells upon target cell recognition, while the majority of CD56bright NK cells produce IFNupon cytokine IL-12 and IL-18 costimulation. A recent study by Yu et al identifies a functional intermediary between CD56bright and CD56dim NK-cell subsets, which is CD56dim phenotype and produces IFNwhen stimulated by target cell (K562) recognition or cytokine costimulation with IL-12 and IL-18.6 This finding provides evidence that CD56bright NK cells might be the precursors of CD56dim IFN–producing cells, which become fully functional in terms of cytokine production and cytotoxicity upon recognition and lysis of cellular targets, including tumor cells. However, further studies are necessary to investigate whether these observations are both developmentally and functionally related. These studies will help us to fully understand the mechanisms of immune differences between CD56bright and CD56dim NK-cell subsets. Acknowledgment: We thank Dr Brian Becknell for critical reading and editing of the manuscript. Conflict-of-interest disclosure: The authors declare no competing financial interests. ■