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 K. Lam, Michael J. Dagley, Eleanor C. 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

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29 Citations (Scopus)


Virtual memory T (TVM) 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 (TMEM) cells, facilitating rapid functionality and survival. Given the semi-differentiated state of TVM cells and their altered functionality with age, here we investigate TVM cell metabolism and its association with longevity and functionality. Elevated SRC is a feature of TVM, but not TMEM, cells and it increases with age in both subsets. The elevated SRC observed in aged mouse TVM 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 TVM, but not TMEM, cells, is driven by physiological levels of IL-15, and is not indicative of enhanced functionality in CD8+ T cells.

Original languageEnglish
Article number2857
Number of pages13
JournalNature Communications
Issue number1
Publication statusPublished - 5 Jun 2020


  • cytotoxic T cells
  • lymphocyte activation

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