The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8+ T Cell Memory and Tumor Immunity
Open accessAbstract
SUMMARY The cell-intrinsic mechanisms guiding naïve CD8+ T cells for clonal expansion and memory generation via Homeostatic Proliferation (HP) are unclear. Herein, we have shown that HP of naïve CD8+ T cells requires IL-7, but not IL-15 induced mTOR kinase activation. HP-induced mTOR enhances transcription factor T-bet for functional maturation and CD122 expression, which sensitizes for an IL-15 dependent memory transition by favoring transcription factor Eomesodermin over T-bet. Inhibition of mTOR blocks T-bet and CD122 expression but preserves memory in an IL-15-independent manner by promoting Eomesodermin expression. The ability of rapamycin to augment HP-induced memory was cell-intrinsic as silencing mTOR in CD8+ T cells generated identical outcomes. Strikingly, HP-induced CD8+ T cell memory generated by IL-15 dependent or independent mechanisms demonstrated identical tumor efficacy. These results indicate a central role for mTOR in HP-induced CD8+ T cell responses and demonstrate the importance for CD8+ memory in HP-induced tumor efficacy.
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Cites
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
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Immunological memory and protective immunity: understanding their relation
Ahmed, R., & Gray, D. (1996) · Science · doi:10.1126/science.272.5258.54 · Cited by 1,775 · cited 1×
“The stimulation of naive CD8+ T cells with antigen, costimulation, and cytokines induce vigorous proliferation and associated differentiation that can give rise to various effector and/or memory phenotypes (Ahmed and Gray, 1996).”
mTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575
Self-citationEnhancing CD8 T-cell memory by modulating fatty acid metabolism
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Homeostasis of Naive and Memory T Cells
Surh, C. D., & Sprent, J. (2008) · Immunity · doi:10.1016/j.immuni.2008.11.002 · Cited by 1,193
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Cited by
Regulation and function of mTOR signalling in T cell fate decisions
Chi, H. (2012) · Nature Reviews Immunology · doi:10.1038/nri3198 · Cited by 1,035
Regulation of Immune Responses by mTOR
Powell, J. D., Pollizzi, K. N., Heikamp, E. B., & Horton, M. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075024 · Cited by 836
Self-citationT memory stem cells in health and disease
Gattinoni, L., Speiser, D. E., Lichterfeld, M., & Bonini, C. (2017) · Nature Medicine · doi:10.1038/nm.4241 · Cited by 620
Klysz, D., Tai, X., Robert, P. A., Craveiro, M., Cretenet, G., Oburoglu, L., Mongellaz, C., Floess, S., Fritz, V., Matias, M. I., et al. (2015) · Science Signaling · doi:10.1126/scisignal.aab2610 · Cited by 522
Signaling by the Phosphoinositide 3-Kinase Family in Immune Cells
Okkenhaug, K. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095946 · Cited by 446
Metadata
- Authors
- Li, Q., Rao, R. R., Araki, K., Pollizzi, K., Odunsi, K., Powell, J. D., & Shrikant, P. A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 34
- Issue
- 4
- Pages
- 541-553
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1982704558
- Cited by
- 161
- References
- 7
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Li, Q., Rao, R. R., Araki, K., Pollizzi, K., Odunsi, K., Powell, J. D., & Shrikant, P. A. (2011). A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8+ T Cell Memory and Tumor Immunity. Immunity. https://doi.org/10.1016/j.immuni.2011.04.006
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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