Age-associated decline in natural killer (NK) activity reflects primarily a defect in function of NK cells

The possible role that natural killer (NK) cells might play in the control of tumors and certain infections prompted an investigation of the status of NK cells in aged mice of two inbred strains (C3H and C57BL/6). The frequency of NK cells in young-adult and aged mice was assessed by two methods that provided accurate estimates of the relative numbers of NK cells: (a) a functional assay procedure from which the number of lytic units could be estimated, and (b) a target-cell (YAC-1 tumor cells) binding procedure. The frequency of NK cells in the spleens of untreated mice as well as in mice infected with Trypanosoma musculi, the latter a powerful NK cell activating agent, was determined. In both strains of mice the frequency of functionally-competent NK cells declined significantly with age, to a greater extent in C3H than in C57BL/6 mice. Similarly, the potential to generate NK cells upon parasite activation was significantly less in aged than in young mice and the reduced potential was more apparent in C3H than in C57BL/6 mice. In contrast, the target cell-binding procedure showed only a modest decline in the frequency of NK cells in the spleens of aged mice of either strain. It appears, therefore, that the decline in NK activity during aging is a reflection of loss of competence to lyse targets rather than a major decline in the actual numbers of NK cells.