A comparison of young and aged NK cells at basal, homeostatic conditions in C57BL/6 mice

Abstract

Elderly people are at greater risk for complications from viral infections. A common explanation is that elderly have compromised immunity. Indeed, conservation of good natural killer (NK) cell cytotoxicity has been correlated with increased survival in later stages in life. Our objective is to examine how ageing affects NK cell homeostasis and their responses to specific stimuli. We use flow cytometric methods to examine the differences among NK cells from adult (6 month) and aged (22 month), male, C57/Bl6 mice. Herein, we show that aged NK cells have functional defects in cytotoxicity and cytokine production. Furthermore, NK cells in primary and secondary lymphoid organs show a skewed immature phenotype with lower acquisition of certain adhesion molecules that provide functional maturation. To identify whether there is a defect on the generation of mature NK cells we compared their developmental stages in the bone marrow of young and aged mice. The numbers of NK cells produced in the bone marrow are not affected by ageing; yet, less mature NK cells are present both in bone marrow as well as in the periphery. Studies on the apoptotic potential of immature and mature NK cells revealed that mature NK cells are more prone for apoptosis in aged mice compared to young, resulting in less mature NK cells. Overall, the homeostasis of mature NK cells in mice is affected by ageing.Support: NIA, Grant R01AG034949.