IL-15 and IL-21 show opposite effects on DNA synthesis and CLL cell survival. (A) Resting or CD40-activated CLL cells were cultured in triplicate wells of 96-well plates in the presence of different concentrations of IL-15 for 48 hours and then pulsed with ³H-thymidine (1 μCi [0.037 MBq]/well) for an additional 18 hours of culture. DNA synthesis by cells cultured in the presence of IL-21 (50 ng/mL) both alone and in combination with IL-15 (50 ng/mL) is also shown. *P < .05 with respect to IL-15 alone. Error bars represent SD. (B) Freshly isolated CLL cells were cultured for 4 days with or without IL-15, IL-21, or a combination of the 2 cytokines (all at 50 ng/mL), and then apoptosis was assessed by the DiOC6 staining method, which determines mitochondrial depolarization. The percentage of apoptotic cells is indicated in each panel.