ArticlePloS one2007
Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.
Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 77 citations in OpenAlex.
- Article
- Two Faces of NFAT Transcription Factors in LymphocytesBiomolecules · 2026Review
- Regulation of TCR-induced Transcriptional Kinetics by Interleukin 2-inducible T Cell Kinase (ITK) in CD8bioRxiv : the preprint server for biology · 2025Article
- Engineered CD4 T cells for in vivo delivery of therapeutic proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Diffusion-limited cytokine signaling in T cell populations.iScience · 2024Article
- Phospho-mimetic CD3ε variants prevent TCR and CAR signaling.Frontiers in immunology · 2024Article
- Primary T-cell-based delivery platform for in vivo synthesis of engineered proteins.Bioengineering & translational medicine · 2024Article
- Antigen perception in T cells by long-term Erk and NFAT signaling dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Modeling Cellular Signaling Variability Based on Single-Cell Data: The TGFβ-SMAD Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Discrete LAT condensates encode antigen information from single pMHC:TCR binding events.Nature communications · 2022Article
- Dapl1 controls NFATc2 activation to regulate CD8Nature cell biology · 2022Article
- Antigen and checkpoint receptor engagement recalibrates T cell receptor signal strength.Immunity · 2021Article
- Hierarchy of signaling thresholds downstream of the T cell receptor and the Tec kinase ITK.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Immunological memory in rheumatic inflammation - a roadblock to tolerance induction.Nature reviews. Rheumatology · 2021Review
- Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells.Journal of immunology research · 2021Article
- Human CD8Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Regulation of T Helper Cell Fate by TCR Signal Strength.Frontiers in immunology · 2020Review
- Mapping the stochastic sequence of individual ligand-receptor binding events to cellular activation: T cells act on the rare events.Science signaling · 2019Article
- Evaluating STAT5 Phosphorylation as a Mean to Assess T Cell Proliferation.Frontiers in immunology · 2019Article
- Peptide Antigen Concentration Modulates Digital NFAT1 Activation in Primary Mouse Naive CD8ImmunoHorizons · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of interleukin-2 (IL-2) is a key event in T helper (Th) lymphocyte activation, controlling both, the expansion and differentiation of effector Th cells as well as the activation of regulatory T cells. We demonstrate that the strength of TCR stimulation is translated into the frequency of memory Th cells expressing IL-2 but not into the amount of IL-2 per cell. This molecular switch decision for IL-2 expression per cell is located downstream of the cytosolic Ca2+ level. Here we show that in a single activated Th cell, NFATc2 activation is digital but NF-kappaB activation is graded after graded T cell receptor (TCR) signaling. Subsequently, NFATc2 translocates into the nucleus in an all-or-none fashion per cell, transforming the strength of TCR-stimulation into the number of nuclei positive for NFATc2 and IL-2 transcription. Thus, the described NFATc2 switch regulates the number of Th cells actively participating in an immune response.
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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.