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

• Published in: Mechanisms of ageing and development 2000-09, Vol.118 (3), p.129-144
• Main Authors: Plett, P.Artur, Gardner, Elizabeth M, Murasko, Donna M
• Format: Article
• Language: English
• Subjects: Aging; Aging - immunology; Analysis of the immune response. Humoral and cellular immunity; Animals; Apoptosis; Biological and medical sciences; Cytotoxicity, Immunologic - immunology; fas Receptor - biosynthesis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Interferon-α/β; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Membrane Proteins; Mice; Mice, Inbred C57BL; NK cells; Organs and cells involved in the immune response; Protein Binding; Receptor, Interferon alpha-beta; Receptors, Interferon - biosynthesis; Receptors, Interferon - metabolism
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/S0047-6374(00)00164-0

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-α/β. The present study explored whether age-related decreases in inducible NK activity after stimulation with IFN-α/β were due to differences in (1) IFN-α/β receptor expression or IFN-α/β binding to NK cells or (2) apoptosis of NK cells. Flow cytometry revealed that, despite significantly higher IFN-α/β receptor expression ( P≤0.03) on NK cells of aged mice, IFN-α/β binding to NK cells was comparable between adult and aged mice. In addition, IFN-α/β treatment significantly increased Fas (CD95) expression ( P≤0.05) on NK cells from both adult and aged mice. However, after IFN-α/β 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-α/β stimulation may include altered IFN-α/β receptors and/or increased percentages of NK cells undergoing apoptosis.