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

doi:10.1038/s41467-020-16633-7

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

Nat Commun. 2020 Jun 5;11(1):2857. doi: 10.1038/s41467-020-16633-7.

Authors

Kylie M Quinn^{1

2}, Tabinda Hussain³, Felix Kraus³, Luke E Formosa³, Wai K Lam³, Michael J Dagley⁴, Eleanor C Saunders⁴, Lisa M Assmus^{3

5}, Erica Wynne-Jones⁶, Liyen Loh⁶, Carolien E van de Sandt^{6

7}, Lucy Cooper³, Kim L Good-Jacobson³, Katherine Kedzierska⁶, Laura K Mackay⁶, Malcolm J McConville⁴, Georg Ramm^{4

8}, Michael T Ryan³, Nicole L La Gruta⁹

Affiliations

¹ Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia. Kylie.quinn@rmit.edu.au.
² School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia. Kylie.quinn@rmit.edu.au.
³ Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
⁴ Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, VIC, 3010, Australia.
⁵ Institute of Experimental Immunology, University Hospital Bonn, 53127, Bonn, Germany.
⁶ Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.
⁷ Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066CX, Amsterdam, Netherlands.
⁸ Monash Ramaciotti Centre for Cryo-EM, Monash University, Clayton, VIC, Australia.
⁹ Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia. Nicole.la.gruta@monash.edu.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aging / immunology*
Animals
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / ultrastructure
Cell Differentiation / immunology
Cell Proliferation
Disease Models, Animal
Female
Humans
Immunologic Memory*
Influenza A virus / immunology
Influenza, Human / blood
Influenza, Human / immunology
Influenza, Human / virology
Male
Mice
Microscopy, Electron, Transmission
Mitochondria / metabolism
Mitochondria / ultrastructure
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism
T-Lymphocyte Subsets / ultrastructure
Young Adult