Metabolic characteristics of CD8+ T cell subsets in young and aged individuals are not predictive of functionality

Abstract

Virtual memory T (T_VM) cells are antigen-naïve CD8⁺ T cells that exist in a semi-differentiated state and exhibit marked proliferative dysfunction in advanced age. High spare respiratory capacity (SRC) has been proposed as a defining metabolic characteristic of antigen-experienced memory T (T_MEM) cells, facilitating rapid functionality and survival. Given the semi-differentiated state of T_VM cells and their altered functionality with age, here we investigate T_VM cell metabolism and its association with longevity and functionality. Elevated SRC is a feature of T_VM, but not T_MEM, cells and it increases with age in both subsets. The elevated SRC observed in aged mouse T_VM cells and human CD8⁺ T cells from older individuals is associated with a heightened sensitivity to IL-15. We conclude that elevated SRC is a feature of T_VM, but not T_MEM, cells, is driven by physiological levels of IL-15, and is not indicative of enhanced functionality in CD8⁺ T cells.