Long-term antigen exposure irreversibly modifies metabolic requirements for T cell function
- Université Libre de Bruxelles, Belgium
- Université Catholique de Louvain, Belgium
Abstract
Energy metabolism is essential for T cell function. However, how persistent antigenic stimulation affects T cell metabolism is unknown. Here, we report that long-term in vivo antigenic exposure induced a specific deficit in numerous metabolic enzymes. Accordingly, T cells exhibited low basal glycolytic flux and limited respiratory capacity. Strikingly, blockade of inhibitory receptor PD-1 stimulated the production of IFNγ in chronic T cells, but failed to shift their metabolism towards aerobic glycolysis, as observed in effector T cells. Instead, chronic T cells appeared to rely on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to produce ATP for IFNγ synthesis. Check-point blockade, however, increased mitochondrial production of superoxide and reduced viability and effector function. Thus, in the absence of a glycolytic switch, PD-1-mediated inhibition appears essential for limiting oxidative metabolism linked to effector function in chronic T cells, thereby promoting survival and functional fitness.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Televie
- Marie Bettonville
- Stefania d'Aria
- Kathleen Weatherly
Interuniversity Attraction Poles
- Pierre Sonveaux
- Michel Y Braun
European Research Council
- Pierre Sonveaux
ARC from Communaute Francaise de Belgique
- Pierre Sonveaux
Fonds De La Recherche Scientifique - FNRS
- Pierre Sonveaux
- Michel Y Braun
Fondation Belge contre le Cancer
- Michel Y Braun
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the European Union Directive 2010/63/EU on the protection of animals used for scientific purposes. All of the animals were handled according to approved institutional animal care and use committee protocols. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Universite Libre de Bruxelles (Protocol Number: 03-2015).
Copyright
© 2018, Bettonville et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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