TY - JOUR
T1 - Apoptosis induced by NK cells is modulated by the NK-active cytokines IL-2 and IL-12
AU - Rodella, Luigi
AU - Rezzani, Rita
AU - Zauli, Giorgio
AU - Mariani, Adriana Rita
AU - Rizzoli, Riccardo
AU - Vitale, Marco
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
KW - EGTA
KW - Fas
KW - Granzyme
KW - K562
KW - Monensin
KW - Peripheral blood lymphocytes
KW - Raji
UR - http://www.scopus.com/inward/record.url?scp=0031840880&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031840880&partnerID=8YFLogxK
U2 - 10.1093/intimm/10.6.719
DO - 10.1093/intimm/10.6.719
M3 - Article
C2 - 9678752
AN - SCOPUS:0031840880
VL - 10
SP - 719
EP - 725
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 6
ER -