The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation
Open accessAbstract
Activation of mTOR-dependent pathways regulates the specification and differentiation of CD4+ T effector cell subsets. Herein, we show that mTOR complex 1 (mTORC1) and mTORC2 have distinct roles in the generation of CD8+ T cell effector and memory populations. Evaluation of mice with a T cell-specific deletion of the gene encoding the negative regulator of mTORC1, tuberous sclerosis complex 2 (TSC2), resulted in the generation of highly glycolytic and potent effector CD8+ T cells; however, due to constitutive mTORC1 activation, these cells retained a terminally differentiated effector phenotype and were incapable of transitioning into a memory state. In contrast, CD8+ T cells deficient in mTORC1 activity due to loss of RAS homolog enriched in brain (RHEB) failed to differentiate into effector cells but retained memory characteristics, such as surface marker expression, a lower metabolic rate, and increased longevity. However, these RHEB-deficient memory-like T cells failed to generate recall responses as the result of metabolic defects. While mTORC1 influenced CD8+ T cell effector responses, mTORC2 activity regulated CD8+ T cell memory. mTORC2 inhibition resulted in metabolic reprogramming, which enhanced the generation of CD8+ memory cells. Overall, these results define specific roles for mTORC1 and mTORC2 that link metabolism and CD8+ T cell effector and memory generation and suggest that these functions have the potential to be targeted for enhancing vaccine efficacy and antitumor immunity.
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Cites
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The PI3K Pathway in Human Disease
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PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer
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The cancer metabolic reprogramming and immune response
Xia, L., Oyang, L., Lin, J., Tan, S., Han, Y., Wu, N., Yi, P., Tang, L., Pan, Q., Rao, S., et al. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01316-8 · Cited by 1,312
Metadata
- Authors
- Pollizzi, K. N., Patel, C. H., Sun, I.-H., Oh, M.-H., Waickman, A. T., Wen, J., Delgoffe, G. M., & Powell, J. D.
- Venue
- Journal of Clinical Investigation
- Published
- 2015-04-20
- Volume
- 125
- Issue
- 5
- Pages
- 2090-2108
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2130746744
- Cited by
- 411
- References
- 18
- FWCI
- 18.28
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pollizzi, K. N., Patel, C. H., Sun, I.-H., Oh, M.-H., Waickman, A. T., Wen, J., Delgoffe, G. M., & Powell, J. D. (2015). mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation. Journal of Clinical Investigation. https://doi.org/10.1172/jci77746
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