Autophagy in T cells from aged donors is maintained by spermidine and correlates with function and vaccine responses.

Autor:	Alsaleh G; The Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, United Kingdom., Panse I; The Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, United Kingdom., Swadling L; Division of Infection and Immunity, University College London, London, United Kingdom., Zhang H; The Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, United Kingdom., Richter FC; The Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, United Kingdom., Meyer A; Fédération de médecine translationnelle Université de Strasbourg, Strasbourg, France., Lord J; MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom., Barnes E; Peter Medawar Building for Pathogen Research,Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.; NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom., Klenerman P; Peter Medawar Building for Pathogen Research,Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.; NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom., Green C; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Simon AK; The Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Dec 15; Vol. 9. Date of Electronic Publication: 2020 Dec 15.
DOI:	10.7554/eLife.57950
Abstrakt:	Vaccines are powerful tools to develop immune memory to infectious diseases and prevent excess mortality. In older adults, however vaccines are generally less efficacious and the molecular mechanisms that underpin this remain largely unknown. Autophagy, a process known to prevent aging, is critical for the maintenance of immune memory in mice. Here, we show that autophagy is specifically induced in vaccine-induced antigen-specific CD8+ T cells in healthy human volunteers. In addition, reduced IFNγ secretion by RSV-induced T cells in older vaccinees correlates with low autophagy levels. We demonstrate that levels of the endogenous autophagy-inducing metabolite spermidine fall in human T cells with age. Spermidine supplementation in T cells from old donors recovers their autophagy level and function, similar to young donors' cells, in which spermidine biosynthesis has been inhibited. Finally, our data show that endogenous spermidine maintains autophagy via the translation factor eIF5A and transcription factor TFEB. In summary, we have provided evidence for the importance of autophagy in vaccine immunogenicity in older humans and uncovered two novel drug targets that may increase vaccination efficiency in the aging context. Competing Interests: GA, IP, LS, HZ, FR, AM, JL, EB, PK, CG, AS No competing interests declared (© 2020, Alsaleh et al.)
Databáze:	MEDLINE
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