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

oleh: Davide Proietto, Beatrice Dallan, Eleonora Gallerani, Valentina Albanese, Sian Llewellyn-Lacey, David A. Price, Victor Appay, Salvatore Pacifico, Antonella Caputo, Francesco Nicoli, Riccardo Gavioli

Format: Article
Diterbitkan: MDPI AG 2023-01-01

Deskripsi

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 <i>in vitro</i> approach to determine how age impacts the generation of <i>de novo</i> CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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.