Ageing curtails the diversity and functionality of nascent CD8 + T cell responses against SARS-CoV-2

Proietto, Davide, Dallan, Beatrice, Gallerani, Eleonora, Albanese, Valentina, Llewellyn-Lacey, Sian, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Appay, Victor, Pacifico, Salvatore, Caputo, Antonella, Nicoli, Francesco and Gavioli, Riccardo 2023. Ageing curtails the diversity and functionality of nascent CD8 + T cell responses against SARS-CoV-2. Vaccines 11 (1) , 154. 10.3390/vaccines11010154

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Abstract

Age-related changes in the immune system are thought to underlie the vulnerability of elderly individuals to emerging viral diseases, such as coronavirus disease 2019 (COVID-19). In this study, we used a fully validated in vitro approach to determine how age impacts the generation of de novo CD8+ T cell responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. Our data revealed a generalized deficit in the ability of elderly individuals to prime the differentiation of naïve precursors into effector CD8+ T cells defined by the expression of interferon (IFN)-γ and the transcription factor T-bet. As a consequence, there was an age-related decline in the diversity of newly generated CD8+ T cell responses targeting a range of typically immunodominant epitopes derived from SARS-CoV-2, accompanied by an overall reduction in the expression frequency of IFN-γ. These findings have potential implications for the development of new strategies to protect the elderly against COVID-19.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	MDPI
Date of First Compliant Deposit:	6 February 2023
Date of Acceptance:	28 December 2022
Last Modified:	06 May 2023 17:17
URI:	https://orca.cardiff.ac.uk/id/eprint/156532

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