Altered basal lipid metabolism underlies the functional impairment of naive CD8+ T cells in elderly humans

Nicoli, Francesco, Cabral-Piccin, Mariela P., Papagno, Laura, Gallerani, Eleonora, Fusaro, Mathieu, Folcher, Victor, Dubois, Marion, Clave, Emmanuel, Vallet, Hélène, Frere, Justin J., Gostick, Emma, Llewellyn-Lacey, Sian, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Toubert, Antoine, Dupré, Loïc, Boddaert, Jacques, Caputo, Antonella, Gavioli, Riccardo and Appay, Victor 2022. Altered basal lipid metabolism underlies the functional impairment of naive CD8+ T cells in elderly humans. The Journal of Immunology 208 (3) , 562–570. 10.4049/jimmunol.2100194

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Abstract

Aging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activation. Importantly, reversal of the bioenergetic anomalies with lipid-altering drugs, such as rosiglitazone, almost completely restored the Ag responsiveness of naive CD8+ T cells. Interventions that favor lipid catabolism may therefore find utility as adjunctive therapies in the elderly to promote vaccine-induced immunity against targetable cancers and emerging pathogens, such as seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Date of First Compliant Deposit:	12 September 2023
Date of Acceptance:	24 November 2021
Last Modified:	04 Oct 2023 11:16
URI:	https://orca.cardiff.ac.uk/id/eprint/162439

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