Autophagy is a critical regulator of memory CD8(+) T cell formation.
During infection, CD8(+) T cells initially expand then contract, leaving a small memory pool providing long lasting immunity. While it has been described that CD8(+) T cell memory formation becomes defective in old age, the cellular mechanism is largely unknown. Autophagy is a major cellular lysosomal degradation pathway of bulk material, and levels are known to fall with age. In this study, we describe a novel role for autophagy in CD8(+) T cell memory formation. Mice lacking the autophagy gene Atg7 in T cells failed to establish CD8(+) T cell memory to influenza and MCMV infection. Interestingly, autophagy levels were diminished in CD8(+) T cells from aged mice. We could rejuvenate CD8(+) T cell responses in elderly mice in an autophagy dependent manner using the compound spermidine. This study reveals a cell intrinsic explanation for poor CD8(+) T cell memory in the elderly and potentially offers novel immune modulators to improve aged immunity.
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Daniel J
DJ
Puleston
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Hanlin
H
Zhang
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Timothy J
TJ
Powell
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Elina
E
Lipina
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
Stuart
S
Sims
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Isabel
I
Panse
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Alexander S
AS
Watson
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Vincenzo
V
Cerundolo
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Alain Rm
AR
Townsend
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
Paul
P
Klenerman
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Anna Katharina
AK
Simon
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D000071193:Autophagy-Related Protein 7; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival; D000939:Epitopes / Q000276:immunology; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000276:immunology*; D018655:Lymphocyte Count; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D014765:Viral Vaccines / Q000276:immunology
C502661:Atg7 protein, mouse; D000939:Epitopes; D051272:Glucose Transporter Type 1; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; C495678:Slc2a1 protein, mouse; D014765:Viral Vaccines; D000071193:Autophagy-Related Protein 7
ageing; autophagy; immunology; influenza; memory T cells; mouse; spermidine; vaccination