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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.
- Source :
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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
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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.
- Subjects :
- Adult
Aged
Female
Humans
Male
Middle Aged
TOR Serine-Threonine Kinases immunology
TOR Serine-Threonine Kinases metabolism
Autophagy immunology
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Glycolysis immunology
Immunologic Memory
Lymphocyte Activation
Subjects
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