Journal article
Age-Related Decline in Primary CD8 T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8 T Cells
KM Quinn, A Fox, KL Harland, BE Russ, J Li, THO Nguyen, L Loh, M Olshanksy, H Naeem, K Tsyganov, F Wiede, R Webster, C Blyth, XYX Sng, T Tiganis, D Powell, PC Doherty, SJ Turner, K Kedzierska, NL La Gruta
Cell Reports | CELL PRESS | Published : 2018
Abstract
Age-associated decreases in primary CD8+ T cell responses occur, in part, due to direct effects on naive CD8+ T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated “virtual memory” (TVM) cells, but their contribution to age-related functional decline is unclear. Here, we show that TVM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (TN cells) retain proliferative capacity in both aged mice and humans. Adoptive transfer experiments in mice illustrated that naive CD8 T cells can ac..
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Grants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Anthony W. Purcell for critical reading of the manuscript, staff at the University of Melbourne and Monash University flow cytometry facilities for excellent technical assistance with cell sorting (Catherine Li, Tina Luke, Angela Hind, Lankesha Yapa, Vanta Jameson, Joshua Kie, Andrew Fryga, Kathryn Flanagan, Michael Reitsma, and Adam Dinsdale), and staff at the University of Melbourne and Monash University animal facilities for excellent animal husbandry of the aged mouse colony, particularly Emily Humphris, Caron Maxim, and Katrina Parr. This work was supported by a Rebecca L. Cooper Medical Research Foundation Grant (to K.M.Q.), a Sylvia and Charles Viertel Senior Medical Research Fellowship (to N.L.L.G.), a National Health and Medical Research Council (NHMRC) Senior Research Fellowship AI1102792 (to K.K.), an NHMRC Program Grant AI1071916 (to N.L.L.G., K.K., S.J.T., and P.C.D.), a Project Grant AI1046333 (to N.L.L.G.), and internal funding from University of Melbourne and Monash University.