Revisiting human natural killer cell subset function revealed cytolytic CD56dimCD16+ NK cells as rapid producers of abundant IFN-γ on activation

A De Maria, F Bozzano, C Cantoni… - Proceedings of the …, 2011 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
The two major functions of human natural killer (NK) cells are conventionally associated with
distinct cell subsets. Thus, cytolytic activity is mostly confined to the CD56dimCD16+ subset,
whereas cytokine production is generally assigned to CD56brightCD16+/− cells. In this
study, we reevaluated the functional capabilities of these NK subsets with regard to the
production of IFN-γ at different time points after cell triggering via NKp46 and NKp30
activating receptors. Different from previous studies, cytokine production was also assessed …
The two major functions of human natural killer (NK) cells are conventionally associated with distinct cell subsets. Thus, cytolytic activity is mostly confined to the CD56dimCD16+ subset, whereas cytokine production is generally assigned to CD56brightCD16+/− cells. In this study, we reevaluated the functional capabilities of these NK subsets with regard to the production of IFN-γ at different time points after cell triggering via NKp46 and NKp30 activating receptors. Different from previous studies, cytokine production was also assessed at early intervals. We show that CD56dim NK cells produce IFN-γ already at 2 to 4 h, whereas no cytokine production is detected beyond 16 h. In contrast, CD56bright cells release IFN-γ only at late time intervals (>16 h after stimulation). The rapid IFN-γ production by CD56dim NK cells is in line with the presence of IFN-γ mRNA in freshly isolated cells. Rapid IFN-γ production was also induced by combinations of IL-2, IL-12, and IL-15. Our data indicate that not only cytolytic activity but also early IFN-γ production is a functional property of CD56dim NK cells. Thus, this subset can assure a rapid and comprehensive NK cell intervention during the early phases of innate responses.
National Acad Sciences