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Distinct energy requirements for human memory CD4 T-cell homeostatic functions
Dennis D Taub1, Charles S Hesdorffer, Luigi Ferrucci
1National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Summary
Energy sources for unactivated CD4 memory T cells (T(mem) cells) differ from activated cells. Fatty acid oxidation (FAO) is crucial for unactivated T(mem) cell trafficking and survival, while glycolysis fuels activated T(mem) cell functions.
Area of Science:
- Immunology
- Cellular Metabolism
Background:
- CD4 memory T cells (T(mem) cells) are vital for adaptive immunity.
- While energy sources for T(mem) cell activation are known, the metabolic requirements for unactivated T(mem) cell maintenance and surveillance are unclear.
Purpose of the Study:
- To investigate the distinct energy sources utilized by unactivated CD4 T(mem) cells for maintenance, trafficking, and survival.
- To compare the metabolic demands of unactivated T(mem) cells with those of activated T(mem) cells.
Main Methods:
- Assessed mitochondrial fatty acid oxidation (FAO) and glycolysis in human unactivated CD4 T(mem) cells.
- Investigated the impact of inhibiting glycolysis or stimulating AMP-activated protein kinase on FAO.
- Examined the effects of CCL19 and sphingosine 1-phosphate (S1P) on FAO and glycolysis.
- Evaluated the role of FAO and glycolysis in T(mem) cell adherence, chemotaxis, and apoptosis.
- Compared energy source utilization between unactivated and activated T(mem) cells.
Main Results:
- Mitochondrial FAO in unactivated CD4 T(mem) cells was enhanced by glycolysis inhibition and AMP-activated protein kinase stimulation, particularly in older individuals.
- CCL19 and S1P minimally affected FAO and glycolysis but were significantly impacted by FAO inhibition for adherence and chemotaxis.
- Inhibition of FAO or glycolysis increased apoptosis under IL-2 deprivation or CCL19 stimulation.
- Activated T(mem) cell chemotaxis to CCL5 relied predominantly on glycolysis, not FAO.
Conclusions:
- Unactivated CD4 T(mem) cells utilize distinct energy pathways for maintenance and surveillance compared to activated cells.
- Fatty acid oxidation is critical for the homeostatic functions of unactivated T(mem) cells, including trafficking and survival.
- Glycolysis is the primary energy source for activated T(mem) cell functions like chemotaxis.
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