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

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

Research output: Contribution to journal › Article › Research › peer-review

36 Citations (Scopus)

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.

Original language	English
Article number	2857
Number of pages	13
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16633-7
Publication status	Published - 5 Jun 2020

Keywords

cytotoxic T cells
lymphocyte activation

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10.1038/s41467-020-16633-7

312287151-oaFinal published version, 2.11 MB

Cite this

Quinn, K. M., Hussain, T., Kraus, F., Formosa, L. E., Lam, W. K., Dagley, M. J., Saunders, E. C., Assmus, L. M., Wynne-Jones, E., Loh, L., van de Sandt, C. E., Cooper, L., Good-Jacobson, K. L., Kedzierska, K., Mackay, L. K., McConville, M. J., Ramm, G., Ryan, M. T., & La Gruta, N. L. (2020). Metabolic characteristics of CD8⁺ T cell subsets in young and aged individuals are not predictive of functionality. Nature Communications, 11(1), Article 2857. https://doi.org/10.1038/s41467-020-16633-7

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

abstract = "Virtual memory T (TVM) cells are antigen-na{\"i}ve 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.",

keywords = "cytotoxic T cells, lymphocyte activation",

author = "Quinn, {Kylie M.} and Tabinda Hussain and Felix Kraus and Formosa, {Luke E.} and Lam, {Wai K.} and Dagley, {Michael J.} and Saunders, {Eleanor C.} and Assmus, {Lisa M.} and Erica Wynne-Jones and Liyen Loh and {van de Sandt}, {Carolien E.} and Lucy Cooper and Good-Jacobson, {Kim L.} and Katherine Kedzierska and Mackay, {Laura K.} and McConville, {Malcolm J.} and Georg Ramm and Ryan, {Michael T.} and {La Gruta}, {Nicole L.}",

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doi = "10.1038/s41467-020-16633-7",

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Quinn, KM, Hussain, T, Kraus, F, Formosa, LE, Lam, WK, Dagley, MJ, Saunders, EC, Assmus, LM, Wynne-Jones, E, Loh, L, van de Sandt, CE, Cooper, L, Good-Jacobson, KL, Kedzierska, K, Mackay, LK, McConville, MJ, Ramm, G , Ryan, MT & La Gruta, NL 2020, 'Metabolic characteristics of CD8⁺ T cell subsets in young and aged individuals are not predictive of functionality', Nature Communications, vol. 11, no. 1, 2857. https://doi.org/10.1038/s41467-020-16633-7

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T1 - Metabolic characteristics of CD8+ T cell subsets in young and aged individuals are not predictive of functionality

AU - Quinn, Kylie M.

AU - Hussain, Tabinda

AU - Kraus, Felix

AU - Formosa, Luke E.

AU - Lam, Wai K.

AU - Dagley, Michael J.

AU - Saunders, Eleanor C.

AU - Assmus, Lisa M.

AU - Wynne-Jones, Erica

AU - Loh, Liyen

AU - van de Sandt, Carolien E.

AU - Cooper, Lucy

AU - Good-Jacobson, Kim L.

AU - Kedzierska, Katherine

AU - Mackay, Laura K.

AU - McConville, Malcolm J.

AU - Ramm, Georg

AU - Ryan, Michael T.

AU - La Gruta, Nicole L.

PY - 2020/6/5

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N2 - 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.

AB - 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.

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

Abstract

Keywords

Access to Document

Other files and links

Publisher Correction: Metabolic characteristics of CD8⁺ T cell subsets in young and aged individuals are not predictive of functionality (Nature Communications, (2020), 11, 1, (2857), 10.1038/s41467-020-16633-7)

Drivers of effective T cell immunity

Limiting the impact of influenza

Animal Research Platform (MARP)

FlowCore

Monash Micro Imaging

Cite this

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

Abstract

Keywords

Access to Document

Other files and links

Research output

Publisher Correction: Metabolic characteristics of CD8+ T cell subsets in young and aged individuals are not predictive of functionality (Nature Communications, (2020), 11, 1, (2857), 10.1038/s41467-020-16633-7)

Projects

Drivers of effective T cell immunity

Limiting the impact of influenza

Equipment

Animal Research Platform (MARP)

FlowCore

Monash Micro Imaging

Cite this

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

Publisher Correction: Metabolic characteristics of CD8⁺ T cell subsets in young and aged individuals are not predictive of functionality (Nature Communications, (2020), 11, 1, (2857), 10.1038/s41467-020-16633-7)