Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8 + T Cells in Elderly Humans - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2022

Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8 + T Cells in Elderly Humans

Justin Frere
David Price

Résumé

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).

Dates et versions

hal-03777022 , version 1 (14-09-2022)

Identifiants

Citer

Francesco Nicoli, Mariela Cabral-Piccin, Laura Papagno, Eleonora Gallerani, Mathieu Fusaro, et al.. Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8 + T Cells in Elderly Humans. Journal of Immunology, 2022, 208 (3), pp.562-570. ⟨10.4049/jimmunol.2100194⟩. ⟨hal-03777022⟩
13 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More