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.

Ageing Curtails the Diversity and Functionality of Nascent CD8+ T Cell Responses against SARS-CoV-2

Davide Proietto
Primo
;
Beatrice Dallan
Secondo
;
Eleonora Gallerani;Valentina Albanese;Salvatore Pacifico;Antonella Caputo;Francesco Nicoli
Penultimo
;
Riccardo Gavioli
Ultimo
2023

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.
2023
Proietto, Davide; Dallan, Beatrice; Gallerani, Eleonora; Albanese, Valentina; Llewellyn-Lacey, Sian; Price, David A.; Appay, Victor; Pacifico, Salvatore; Caputo, Antonella; Nicoli, Francesco; Gavioli, Riccardo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2500960
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