ArticleThe Journal of experimental medicine2013
N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T cell memory but not to effector differentiation.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- CD4Cell death & disease · 2022Trial
- T-helper cells flexibility: the possibility of reprogramming T cells fate.Frontiers in immunology · 2023Review
- Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- Kras-Deficient T Cells Attenuate Graft-versus-Host Disease but Retain Graft-versus-Leukemia Activity.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Small GTPase RAS in multiple sclerosis - exploring the role of RAS GTPase in the etiology of multiple sclerosis.Small GTPases · 2020Review
- Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development.Experimental & molecular medicine · 2020Review
- Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity.PLoS biology · 2020Article
- Concomitant deletion of HRAS and NRAS leads to pulmonary immaturity, respiratory failure and neonatal death in mice.Cell death & disease · 2019Article
- Genealogy, Dendritic Cell Priming, and Differentiation of Tissue-Resident Memory CD8Frontiers in immunology · 2018Review
- Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein.PLoS neglected tropical diseases · 2017Article
- TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines.Current opinion in immunology · 2017Review
- PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas.Scientific reports · 2017Article
- Optimal Generation of Tissue-Resident but Not Circulating Memory T Cells during Viral Infection Requires Crosspriming by DNGR-1Immunity · 2016Article
- Unexpected positive control of NFκB and miR-155 by DGKα and ζ ensures effector and memory CD8+ T cell differentiation.Oncotarget · 2016Article
- Kras Is Critical for B Cell Lymphopoiesis.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Diacylglycerol Kinases in T Cell Tolerance and Effector Function.Frontiers in cell and developmental biology · 2016Review
- The tyrosine kinase Itk suppresses CD8+ memory T cell development in response to bacterial infection.Scientific reports · 2015Article
- TCR Signaling in T Cell Memory.Frontiers in immunology · 2015Review
- Article
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signals from the TCR that specifically contribute to effector versus memory CD8⁺ T cell differentiation are poorly understood. Using mice and adoptively transferred T lymphocytes lacking the small GTPase N-ras, we found that N-ras-deficient CD8⁺ T cells differentiate efficiently into antiviral primary effectors but have a severe defect in generating protective memory cells. This defect was rescued, although only partly, by rapamycin-mediated inhibition of mammalian target of rapamycin (mTOR) in vivo. The memory defect correlated with a marked impairment in vitro and in vivo of the antigen-mediated early induction of T-box transcription factor Eomesodermin (Eomes), whereas T-bet was unaffected. Besides N-ras, early Eomes induction in vitro required phosphoinositide 3-kinase (PI3K)-AKT but not extracellular signal-regulated kinase (ERK) activation, and it was largely insensitive to rapamycin. Consistent with N-ras coupling Eomes to T cell memory, retrovirally enforced expression of Eomes in N-ras-deficient CD8⁺ T cells effectively rescued their memory differentiation. Thus, our study identifies a critical role for N-ras as a TCR-proximal regulator of Eomes for early determination of the CD8⁺ T cell memory fate.
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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 OpenQuestion graph.