The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin
What this study shows
Working with naive OT-I CD8 T cells stimulated by antigen plus B7.1, the authors showed that IL-12 both raised and prolonged mTOR phosphorylation and S6K1 Thr389 phosphorylation out to 48 hours, and that this required PI3K throughout and STAT4 for the late phase. Rapamycin, added at the start or only at 12 hours, blocked the sustained expression of T-bet and with it the heritable type I effector programme, while raising Eomesodermin and producing cells with a memory-precursor phenotype (CD62L high, KLRG1 low, Bcl-2 high). Restoring T-bet by a tamoxifen-inducible construct brought back IFN-gamma production and lowered Eomesodermin, which places T-bet downstream of mTOR in this system. After transfer, the rapamycin-treated cells persisted better, gave stronger antigen-recall responses, and more than 78 percent of recipients stayed tumour-free to day 120 against 50 percent fatality with IL-12-conditioned effector cells. Boundary: mouse CD8 T cells, one TCR-transgenic system with pharmacological mTOR inhibition in vitro before transfer; the transplantable E.G7 tumour is a model, not a treatment result in people, and the memory-precursor phenotype faded by day 40 after transfer.
At a glance
| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Naive mouse OT-I CD8 T cells (and STAT4-deficient OT-I) stimulated in vitro with antigen plus B7.1 and IL-12, with rapamycin, PI3K inhibition, insulin or 2-deoxyglucose; adoptive transfer into C57BL/6 recipients and E.G7 tumour challenge) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Naive mouse OT-I CD8 T cells (and STAT4-deficient OT-I) stimulated in vitro with antigen plus B7.1 and IL-12, with rapamycin, PI3K inhibition, insulin or 2-deoxyglucose; adoptive transfer into C57BL/6 recipients and E.G7 tumour challenge |
| Journal | Immunity |
| Year | 2010 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1016/j.immuni.2009.10.010 · PMID 20060330 · Free full text (PMC5836496) |
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 | Rapamycin during in vitro antigen plus IL-12 conditioning; PI3K inhibitor LY294002; insulin; 2-deoxyglucose; STAT4 deficiency; inducible T-bet |
| Target | mTORC1 (S6K1/S6 phosphorylation), T-bet and Eomesodermin expression in CD8 T cells |
| Model | Mouse |
| Effect | mTOR inhibition lowered sustained T-bet and effector function and raised Eomesodermin and memory-precursor features |
In the Atlas
Related topics
Links in the pathway map
- Supports mTORC1 activates S6K1
- Supports Rapamycin inhibits mTORC1
More studies on this topic
- Regulation and function of mTOR signalling in T cell fate decisions (2012)
- The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment (2009)
- The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2 (2011)
- L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity (2016)
Thank you. Your answer was counted anonymously.