Genetic differences in the age-associated decrease in inducibility of natural killer cells by interferon-alpha/beta.
Natural killer (NK) cells, which are important in viral infections and anti-tumor activity, show reduced cytotoxicity in aged mice. The mechanism(s) for this age-related decline in NK activity has not been clearly established. We assessed changes in NK cytotoxicity in splenocytes and peripheral blood mononuclear cells after interferon (IFN)-alpha/beta stimulation in adult (6 months) and aged (22-26 months) C57Bl/6, Balb/c, and (Balb/c x C57Bl/6)F1 mice. Aged C57Bl/6 and Balb/c mice had a significantly reduced IFN-alpha/beta-stimulated NK cytotoxicity compared to adult mice. In contrast, adult and aged F1 mice showed similar NK cytotoxicity after IFN-alpha/beta induction. The decreased ability of NK cells of aged mice to respond to induction by IFN-alpha/beta was not due to a requirement for an increased amount of IFN or for a longer period of treatment with IFN. Further, this decreased response did not appear to be the result of suppressive activity of adherent cells or T cells. While the percentage of NK cells (NK1.1+) was similar in adult and aged mice, the (CD8+ NK1.1+) subset of NK cells was significantly increased in aged mice. Importantly, the percentage of CD8+ NK1.1+ cells was inversely related to the cytotoxicity observed after IFN-alpha/beta treatment.
Plett
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Department of Microbiology and Immunology, MCP Hahnemann University School of Medicine, Philadelphia, PA 19129, USA.
Murasko
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D000375:Aging / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology; D011994:Recombinant Proteins; D013045:Species Specificity; D014018:Tissue Distribution
D007369:Interferon Inducers; D007370:Interferon Type I; D011994:Recombinant Proteins; D011070:Poly I-C