Journal article

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

Nature Communications | NATURE PUBLISHING GROUP | Published : 2020

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..

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Grants

Awarded by Australian Research Council (ARC)


Awarded by National Health and Medical Research Council (NHMRC) Program


Awarded by Bonn and Melbourne Research and Graduate School


Awarded by European Union's Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant


Awarded by NHMRC Senior Research Fellowship Level B


Funding Acknowledgements

We thank Adam Costin and Joan Clark for technical assistance in electron microscopy, and staff at Monash University Ramaciotti Centre for Cryo-Electron Microscopy, Monash University FlowCore, Monash Micro Imaging, and Monash University Animal Facilities. This work was supported by a Sylvia and Charles Viertel Senior Medical Research Fellowship, an Australian Research Council (ARC) Future Fellowship FT170100174, a National Health and Medical Research Council (NHMRC) Program grant APP1071916 (to N.L.L.), a Rebecca L. Cooper Foundation Medical Research Grant (to K.M.Q), a Viertel-Belberry Senior Medical Research Fellowship (to K.L.G.-J.), Monash Graduate Scholarship and Monash International Postgraduate Research Scholarship (to T.H.) a Monash University Biomedicine Discovery Scholarship (to L.C.) and funding from the Bonn and Melbourne Research and Graduate School (GRK2168). C.E.S. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant agreement No. 792532 and University of Melbourne McKenzie Fellowship laboratory support. KK is supported by a NHMRC Senior Research Fellowship Level B (GNT#1102792).