Enhancing CD8 T-cell memory by modulating fatty acid metabolism
What this study shows
Mice whose T cells lacked the adaptor protein TRAF6 mounted a normal effector CD8 T-cell response to Listeria infection, but the antigen-specific cells vanished during contraction and almost no memory cells formed. The TRAF6-deficient cells failed to activate AMPK and mitochondrial fatty acid oxidation when the growth factor IL-2 was withdrawn. Daily metformin restored fatty acid oxidation and memory formation, and also raised memory CD8 T-cell numbers in normal mice: in a tumour vaccine model 6 of 9 metformin-treated mice survived beyond day 33 against 1 of 8 controls. Daily rapamycin (1.5 mg/kg), used as a second drug that promotes fatty acid oxidation, likewise increased memory CD8 T-cell development and recall responses. Boundary: mouse only, one bacterial infection model and one transplantable tumour; the rapamycin arm is a secondary experiment and mTOR activity itself was not measured in these cells.
At a glance
| Evidence type | A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mice with T-cell-specific TRAF6 deletion (CD4-cre), OT-I TCR-transgenic adoptive transfer, Listeria monocytogenes-OVA infection, EL4-OVA tumour vaccine model, and activated mouse CD8 T cells in vitro after IL-2 withdrawal); the code names the system studied -- animal work can be rigorous and still not be human data. |
| Study type | 4 - Animal Study |
| Model system | Mice with T-cell-specific TRAF6 deletion (CD4-cre), OT-I TCR-transgenic adoptive transfer, Listeria monocytogenes-OVA infection, EL4-OVA tumour vaccine model, and activated mouse CD8 T cells in vitro after IL-2 withdrawal |
| Journal | Nature |
| Year | 2009 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1038/nature08097 · PMID 19494812 · Free full text (PMC2803086) |
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | T-cell-specific TRAF6 deletion; daily metformin (250 mg/kg); daily rapamycin (1.5 mg/kg) |
| Target | CD8 T-cell fatty acid oxidation and memory formation |
| Model | Mouse |
| Effect | TRAF6 loss abolished CD8 memory formation; metformin or rapamycin increased memory CD8 T cells, and metformin improved anti-tumour vaccine protection |
In the Atlas
Related topics
Links in the pathway map
- Supports Metformin activates AMPK
More studies on this topic
- Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets (2011)
- Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state (2010)
- Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex (2017)
- Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner (2010)
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