Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8+ T Cells in Elderly Humans.
J Immunol
; 208(3): 562-570, 2022 02 01.
Article
in English
| MEDLINE | ID: covidwho-1625582
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).
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Aging
/
CD8-Positive T-Lymphocytes
/
Lipid Metabolism
/
Immunocompetence
Type of study:
Randomized controlled trials
Topics:
Vaccines
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
/
Young adult
Language:
English
Journal:
J Immunol
Year:
2022
Document Type:
Article
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