Metabolic characteristics of CD8+ T cell subsets in young and aged individuals are not predictive of functionality
Kylie M. Quinn, Tabinda Hussain, Felix Kraus, Luke E. Formosa, Wai Kit Lam, Michael J. Dagley, Eleanor Saunders, Lisa M. Assmus, Erica Wynne-Jones, Liyen Loh, Carolien E. van de Sandt, Lucy Cooper, Kim L. Good‐Jacobson, Katherine Kedzierska, Laura K. Mackay, Malcolm J. McConville, Georg Ramm, Michael T. Ryan, Nicole L. La Gruta
Abstract
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.