Ageing and inflammation limit the induction of SARS-CoV-2-specific CD8+ T cell responses in severe COVID-19

Autaa, Gaëlle, Papagno, Laura, Nogimori, Takuto, Boizard-Moracchini, Andrea, Korenkov, Daniil, Roy, Maeva, Suzuki, Koichiro, Masuta, Yuji, White, Eoghann, Llewellyn-Lacey, Sian, Yoshioka, Yasuo, Nicoli, Francesco, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Dechanet-Merville, Julie, Yamamoto, Takuya, Pellegrin, Isabelle and Appay, Victor 2025. Ageing and inflammation limit the induction of SARS-CoV-2-specific CD8+ T cell responses in severe COVID-19. JCI Insight 10 (4) , e180867. 10.1172/jci.insight.180867

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Abstract

CD8+ T cells are critical for immune protection against severe COVID-19 during acute infection with SARS-CoV-2. However, the induction of antiviral CD8+ T cell responses varies substantially among infected people, and a better understanding of the mechanisms that underlie such immune heterogeneity is required for pandemic preparedness and risk stratification. In this study, we analyzed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in relation to age, clinical status, and inflammation among patients infected primarily during the initial wave of the pandemic in France or Japan. We found that age-related contraction of the naive lymphocyte pool and systemic inflammation were associated with suboptimal SARS-CoV-2-specific CD4+ and, even more evidently, CD8+ T cell immunity in patients with acute COVID-19. No such differences were observed for humoral immune responses targeting the spike protein of SARS-CoV-2. We also found that the proinflammatory cytokine IL-18, concentrations of which were significantly elevated among patients with severe disease, suppressed the de novo induction and memory recall of antigen-specific CD8+ T cells, including those directed against SARS-CoV-2. These results potentially explain the vulnerability of older adults to infections that elicit a profound inflammatory response, exemplified by acute COVID-19.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	American Society for Clinical Investigation
ISSN:	2379-3708
Date of First Compliant Deposit:	30 January 2025
Date of Acceptance:	23 January 2025
Last Modified:	05 Mar 2025 14:03
URI:	https://orca.cardiff.ac.uk/id/eprint/175747

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