NK cells kill sensitive targets via exocytosis of cytoplasmic granules containing membrane damaging perforins and DNA damaging granzymes. Therefore, the target cell can either die by necrosis or by apoptosis. A third, non-secretory, mechanism of killing mediated by Fas-FasL interaction can be used by activated NK cells to kill Fas+ targets. Here, we have studied the modulation exerted by two NK active cytokines, IL-2 and IL-12, on the apoptosis-inducing activity of NK cells in NK-sensitive Fas- K562 and NK-insensitive Fas+ Raji cells. Our results show that apoptosis is preferentially induced at low target:effector ratios. Resting NK cells virtually do not induce apoptosis in target cells while IL-2 stimulation endows NK cells with the capacity of inducing apoptosis and IL-12 further enhances this effect against both targets. Finally, we demonstrate that cytokine-stimulated NK cells use both granzyme and Fas-FasL pathways of apoptosis induction.
Apoptosis induced by NK cells is modulated by the NK-active cytokines IL-2 andIL-12 / RODELLA L.; REZZANI R.; ZAULI G.; MARIANI AR.; RIZZOLI R.; VITALE M.. - In: INTERNATIONAL IMMUNOLOGY. - ISSN 0953-8178. - 10(6)(1998), pp. 719-725. [10.1093/intimm/10.6.719]