ArticleThe Journal of clinical investigation2015
mTORC1 and mTORC2 selectively regulate CD8⁺ T cell differentiation.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers.
What it found
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The trial behind it
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Who cites it
262 citing papers in PubMed.
- mTOR Inhibitor Therapy Diminishes Circulating CD8+ CD28- Effector Memory T Cells and Improves Allograft Inflammation in Belatacept-refractory Renal Allograft Rejection.Transplantation · 2020Trial
- mTORC1 inhibition upregulates CD20 and enhances anti-CD20 antibody efficacy in B-cell precursor acute lymphoblastic leukemia.Leukemia · 2026Article
- CD8Cell reports. Medicine · 2026Review
- Exploratory Analysis of Autophagy-related Genes and Immune Infiltration in Human Hippocampal Tissue of Temporal Lobe Epilepsy.Molecular neurobiology · 2026Article
- Identification of the novel therapeutic target gene SLC12A9, which determines the prognosis of patients with colorectal cancer.Surgery today · 2026Article
- Coadministration of rapamycin with a DNA/MVA SIV vaccine improves memory CD8+ T cell response.JCI insight · 2026Article
- Immunosenescence and Vaccine Efficacy in Aging: Dynamic Interplay of Gut Microbiota and mTOR Signaling Pathways.Aging cell · 2026Review
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review).International journal of molecular medicine · 2026Review
- mTOR signaling regulates demand-adapted hematopoiesis and metabolic reprogramming required for an effective cellular immune response in Drosophila melanogaster larvae.PLoS genetics · 2026Article
- Tissue-distinct Features of Follicular Cytotoxic CD8bioRxiv : the preprint server for biology · 2026Article
- Active aldehydes accelerate CD8Nature immunology · 2026Article
- T Cell Exhaustion in Hepatocellular Carcinoma: A Substantial Barrier in Immunotherapy.Journal of cellular and molecular medicine · 2026Review
- Article
- Glucose availability tunes latent CD8+ T cell expansion potential through a mitogen-independent, mTOR-dependent regulatory switch.bioRxiv : the preprint server for biology · 2026Article
- Aminoacyl-tRNA synthetases in tumor immunity: canonical translation, source-resolved immune circuits and therapeutic opportunities.Frontiers in immunology · 2026Review
- Autophagy-regulated mitochondrial inheritance controls early CD8Nature cell biology · 2026Article
- Unraveling the pleiotropic roles of the mTOR-glycolytic axis in ulcerative colitis: from immunometabolic dysregulation to mucosal barrier remodeling.Frontiers in immunology · 2026Review
- Mitochondrial complex II orchestrates divergent effects in CD4+ and CD8+ T cells.The Journal of clinical investigation · 2025Article
- Defining Microbiota-Derived Metabolite Butyrate as a Senomorphic: Therapeutic Potential in the Age-Related T Cell Senescence.Aging cell · 2025Article
202 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.