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 and Nicole L. La Gruta ()
Additional contact information
Kylie M. Quinn: Monash Biomedicine Discovery Institute, Monash University
Tabinda Hussain: Monash Biomedicine Discovery Institute, Monash University
Felix Kraus: Monash Biomedicine Discovery Institute, Monash University
Luke E. Formosa: Monash Biomedicine Discovery Institute, Monash University
Wai K. Lam: Monash Biomedicine Discovery Institute, Monash University
Michael J. Dagley: University of Melbourne
Eleanor C. Saunders: University of Melbourne
Lisa M. Assmus: Monash Biomedicine Discovery Institute, Monash University
Erica Wynne-Jones: University of Melbourne, Peter Doherty Institute for Infection and Immunity
Liyen Loh: University of Melbourne, Peter Doherty Institute for Infection and Immunity
Carolien E. van de Sandt: University of Melbourne, Peter Doherty Institute for Infection and Immunity
Lucy Cooper: Monash Biomedicine Discovery Institute, Monash University
Kim L. Good-Jacobson: Monash Biomedicine Discovery Institute, Monash University
Katherine Kedzierska: University of Melbourne, Peter Doherty Institute for Infection and Immunity
Laura K. Mackay: University of Melbourne, Peter Doherty Institute for Infection and Immunity
Malcolm J. McConville: University of Melbourne
Georg Ramm: University of Melbourne
Michael T. Ryan: Monash Biomedicine Discovery Institute, Monash University
Nicole L. La Gruta: Monash Biomedicine Discovery Institute, Monash University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-16633-7

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