Age-related changes in interferon-alpha/beta receptor expression, binding, and induction of apoptosis in natural killer cells from C57BL/6 mice.

Natural killer (NK) cells are a critical first line of defense against viral infections and tumors. We showed previously that basal NK cytotoxicity was comparable in adult (6 month) and aged (24 month) C57BL/6 (B6) mice. However, NK activity was significantly higher in adult compared with aged B6 mice after either in vitro or in vivo stimulation with IFN-alpha/beta. The present study explored whether age-related decreases in inducible NK activity after stimulation with IFN-alpha/beta were due to differences in (1) IFN-alpha/beta receptor expression or IFN-alpha/beta binding to NK cells or (2) apoptosis of NK cells. Flow cytometry revealed that, despite significantly higher IFN-alpha/beta receptor expression (P</=0.03) on NK cells of aged mice, IFN-alpha/beta binding to NK cells was comparable between adult and aged mice. In addition, IFN-alpha/beta treatment significantly increased Fas (CD95) expression (P</=0.05) on NK cells from both adult and aged mice. However, after IFN-alpha/beta stimulation, NK cells from aged mice demonstrated significantly higher CD95 expression (P</=0.03) and percent apoptosis (P</=0.05) relative to adult mice. These results suggest possible mechanisms for age-associated decreases in inducible NK cytotoxicity after IFN-alpha/beta stimulation may include altered IFN-alpha/beta receptors and/or increased percentages of NK cells undergoing apoptosis.