RESUMEN
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).
Asunto(s)
Envejecimiento/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunocompetencia/efectos de los fármacos , Metabolismo de los Lípidos , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Linfocitos T CD8-positivos/metabolismo , COVID-19/inmunología , Vacunas contra el Cáncer/inmunología , División Celular , Femenino , Fenofibrato/farmacología , Glucosa/metabolismo , Antígeno HLA-A2/inmunología , Humanos , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Gripe Humana/inmunología , Metabolismo de los Lípidos/efectos de los fármacos , Activación de Linfocitos , Antígeno MART-1/química , Antígeno MART-1/inmunología , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Fragmentos de Péptidos/inmunología , Rosiglitazona/farmacología , Método Simple Ciego , Vacunación , Vacunas Virales/inmunología , Adulto JovenRESUMEN
Fenofibrate, which is a PPAR-alfpha agonist, increases the level of sulfatide. In this letter we hypothesize on the background of various findings that this is beneficial against COVID-19. Fenofibrate has been used for decades against hypercholesterolemia and has no serious side effects. Therefore, a trial giving fenofibrate to patients with corona virus infection is recommended.