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Naïve CD8 + T-Cells Engage a Versatile Metabolic Program Upon Activation in Humans and Differ Energetically From Memory CD8 + T-Cells.

Authors :
Nicoli F
Papagno L
Frere JJ
Cabral-Piccin MP
Clave E
Gostick E
Toubert A
Price DA
Caputo A
Appay V
Source :
Frontiers in immunology [Front Immunol] 2018 Dec 21; Vol. 9, pp. 2736. Date of Electronic Publication: 2018 Dec 21 (Print Publication: 2018).
Publication Year :
2018

Abstract

Background: Characterization of the intracellular biochemical processes that regulate the generation and maintenance of effector and memory CD8 <superscript>+</superscript> T-cells from naïve precursors is essential for our understanding of adaptive immune responses and the development of immunotherapies. However, the metabolic determinants of antigen-driven activation and differentiation remain poorly defined, especially in humans. Methods: We used a variety of different approaches, including gene expression profiling and measurements of nutrient flux, to characterize the basal and activation-induced energetic requirements of naïve and phenotypically-defined subsets of human memory CD8 <superscript>+</superscript> T-cells. Findings: Profound metabolic differences were apparent as a function of differentiation status, both at rest and in response to stimulation via the T cell receptor (TCR). Of particular note, resting naïve CD8 <superscript>+</superscript> T cells were largely quiescent, but rapidly upregulated diverse energetic pathways after ligation of surface-expressed TCRs. Moreover, autophagy and the mechanistic target of rapamycin (mTOR)-dependent glycolytic pathway were identified as critical mediators of antigen-driven priming in the naïve CD8 <superscript>+</superscript> T cell pool, the efficiency of which was dampened by the presence of neutral lipids and fatty acids. Interpretation: These observations provide a metabolic roadmap of the CD8 <superscript>+</superscript> T-cell compartment in humans and reveal potentially selective targets for novel immunotherapies.

Details

Language :
English
ISSN :
1664-3224
Volume :
9
Database :
MEDLINE
Journal :
Frontiers in immunology
Publication Type :
Academic Journal
Accession number :
30619240
Full Text :
https://doi.org/10.3389/fimmu.2018.02736