Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8 + T Cells in Elderly Humans
Francesco Nicoli
(1, 2)
,
Mariela Cabral-Piccin
(1)
,
Laura Papagno
(1)
,
Eleonora Gallerani
(2)
,
Mathieu Fusaro
(3)
,
Victor Folcher
(1)
,
Marion Dubois
(1)
,
Emmanuel Clave
(4)
,
Hélène Vallet
(1, 5)
,
Justin Frere
(6)
,
Emma Gostick
(7)
,
Sian Llewellyn-Lacey
(7)
,
David Price
(7)
,
Antoine Toubert
(4, 8)
,
Loïc Dupré
(3, 9, 10)
,
Jacques Boddaert
(1, 5)
,
Antonella Caputo
(2)
,
Riccardo Gavioli
(2)
,
Victor Appay
(1, 11, 12)
1
CIMI -
Centre d'Immunologie et des Maladies Infectieuses
2 UniFE - Università degli Studi di Ferrara = University of Ferrara
3 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
4 EMily (UMR_S_1160 / U1160) - Ecotaxie, microenvironnement et développement lymphocytaire
5 CHU Pitié-Salpêtrière [AP-HP]
6 University of Arizona
7 School of Medicine [Cardiff]
8 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
9 LBI-RUD - Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
10 Medizinische Universität Wien = Medical University of Vienna
11 Kumamoto University
12 ImmunoConcept - Immunology from Concept and Experiments to Translation
2 UniFE - Università degli Studi di Ferrara = University of Ferrara
3 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
4 EMily (UMR_S_1160 / U1160) - Ecotaxie, microenvironnement et développement lymphocytaire
5 CHU Pitié-Salpêtrière [AP-HP]
6 University of Arizona
7 School of Medicine [Cardiff]
8 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
9 LBI-RUD - Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
10 Medizinische Universität Wien = Medical University of Vienna
11 Kumamoto University
12 ImmunoConcept - Immunology from Concept and Experiments to Translation
Mariela Cabral-Piccin
- Fonction : Auteur
- PersonId : 1164379
- ORCID : 0000-0003-2914-9610
Victor Folcher
- Fonction : Auteur
- PersonId : 1164380
- ORCID : 0000-0001-7599-3658
Emmanuel Clave
- Fonction : Auteur
- PersonId : 1150441
- ORCID : 0000-0001-8217-5039
Hélène Vallet
- Fonction : Auteur
- PersonId : 1197639
- IdHAL : helene-vallet
- ORCID : 0000-0002-3593-5055
- IdRef : 185807992
David Price
- Fonction : Auteur
- PersonId : 1164382
- ORCID : 0000-0001-9416-2737
Antoine Toubert
- Fonction : Auteur
- PersonId : 777187
- ORCID : 0000-0002-7308-7317
- IdRef : 053430816
Loïc Dupré
- Fonction : Auteur
- PersonId : 803318
- ORCID : 0000-0002-7278-6503
- IdRef : 121589501
Antonella Caputo
- Fonction : Auteur
- PersonId : 1164383
- ORCID : 0000-0002-1241-0299
Riccardo Gavioli
- Fonction : Auteur
- PersonId : 1164384
- ORCID : 0000-0002-7805-4290
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).