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

Alsaleh, G; Panse, I; Swadling, L; Zhang, H; Richter, FC; Meyer, A; Lord, J; ... Simon, AK; + view all (2020) Autophagy in T cells from aged donors is maintained by spermidine and correlates with function and vaccine responses. eLife , 9 , Article e57950. 10.7554/eLife.57950. Green open access

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Abstract

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.

Type: Article
Title: Autophagy in T cells from aged donors is maintained by spermidine and correlates with function and vaccine responses
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.57950
Publisher version: http://dx.doi.org/10.7554/eLife.57950
Language: English
Additional information: Copyright Alsaleh et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: TFEB, autophagy, human, human T cells, immunology, inflammation, spermidine, vaccine
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10119007
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