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Updated: May 16, 2026
06:07
Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
Published on: March 28, 2025
FAS-controlled T cells drive lymphoproliferation through glycolysis without effector differentiation.
Maria Elena Maccari1,2, Christoph König1,3, Geoffroy Andrieux4
1Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Journal of Human Immunity
|May 15, 2026
Summary
Autoimmune lymphoproliferative syndrome (ALPS) involves highly proliferative T cells. These cells exhibit high glycolysis, but unlike virus-activated cells, they do not differentiate or produce IFNγ.
Area of Science:
- Immunology
- Cell Metabolism
Background:
- Autoimmune lymphoproliferative syndrome (ALPS) is characterized by lymphoproliferation driven by FAS-deficient T cells (FCT).
- The metabolic fuels and activating signals driving FCT proliferation remain poorly understood.
- Acute Epstein-Barr virus (EBV) infection also causes lymphoproliferation via proliferative T cells, which utilize a metabolic switch to glycolysis for effector functions.
Purpose of the Study:
- To characterize the metabolic profile of FCT from ALPS patients.
- To compare FCT metabolism with EBV-induced CD8 effector T cells.
Main Methods:
- Metabolic assays
- RNA sequencing
- In silico computational analysis
- Comparison with EBV-induced T cells
Main Results:
- FCT exhibit high glycolysis, similar to EBV-induced effector T cells.
- FCT glycolysis is uncoupled from T-BET expression and IFNγ production.
- FCT display mitochondrial hyperpolarization and increased reactive oxygen species (ROS) production, unlike virus-activated T cells.
Conclusions:
- FCT lymphoproliferation is driven by enhanced glycolysis due to activating signals.
- This glycolytic program in FCT does not lead to classical T cell effector differentiation or IFNγ production.
- ALPS T cell proliferation follows a distinct metabolic pathway compared to antiviral T cells.
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