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Nature Research, Nature Communications, 1(11), 2020

DOI: 10.1038/s41467-020-16633-7

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

Journal article published in 2020 by Kylie M. Quinn ORCID, Tabinda Hussain ORCID, Felix Kraus, Luke E. Formosa ORCID, Wai K. Lam ORCID, Michael J. Dagley ORCID, Eleanor C. Saunders, Lisa M. Assmus ORCID, Erica Wynne-Jones, Liyen Loh ORCID, Carolien E. van de Sandt ORCID, Lucy Cooper ORCID, Kim L. Good-Jacobson ORCID, Katherine Kedzierska ORCID, Laura K. Mackay ORCID and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractVirtual 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.