ArticleeLife2014
T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks.
Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed.
- Article
- T cell decision-making decodes the dynamic antigenic landscape.Frontiers in immunology · 2026Review
- Diffusion-limited cytokine signaling in T cell populations.iScience · 2024Article
- Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells.Immunotherapy advances · 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
- T cell receptor and IL-2 signaling strength control memory CD8Nature communications · 2022Article
- Intrinsic IL-2 production by effector CD8 T cells affects IL-2 signaling and promotes fate decisions, stemness, and protection.Science immunology · 2022Article
- The interplay between membrane topology and mechanical forces in regulating T cell receptor activity.Communications biology · 2022Review
- Divide and Conquer: Phenotypic and Temporal Heterogeneity Within CD8Frontiers in immunology · 2022Review
- Staggered starts in the race to T cell activation.Trends in immunology · 2021Review
- Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction.Scientific reports · 2021Article
- Article
- Regulation of T Helper Cell Fate by TCR Signal Strength.Frontiers in immunology · 2020Review
- Order by chance: origins and benefits of stochasticity in immune cell fate control.Current opinion in systems biology · 2019Article
- Modeling cell-cell communication for immune systems across space and time.Current opinion in systems biology · 2019Review
- Peripheral immune response in the African green monkey model following Nipah-Malaysia virus exposure by intermediate-size particle aerosol.PLoS neglected tropical diseases · 2019Article
- TCR Affinity Biases Th Cell Differentiation by Regulating CD25, Eef1e1, and Gbp2.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Cytokine-mediated communication: a quantitative appraisal of immune complexity.Nature reviews. Immunology · 2019Review
- T cell cytolytic capacity is independent of initial stimulation strength.Nature immunology · 2018Article
- Expression variation and covariation impair analog and enable binary signaling control.Molecular systems biology · 2018Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Variability within isogenic T cell populations yields heterogeneous 'local' signaling responses to shared antigenic stimuli, but responding clones may communicate 'global' antigen load through paracrine messengers, such as cytokines. Such coordination of individual cell responses within multicellular populations is critical for accurate collective reactions to shared environmental cues. However, cytokine production may saturate as a function of antigen input, or be dominated by the precursor frequency of antigen-specific T cells. Surprisingly, we found that T cells scale their collective output of IL-2 to total antigen input over a large dynamic range, independently of population size. Through experimental quantitation and computational modeling, we demonstrate that this scaling is enforced by an inhibitory cross-talk between antigen and IL-2 signaling, and a nonlinear acceleration of IL-2 secretion per cell. Our study reveals how time-integration of these regulatory loops within individual cell signaling generates scaled collective responses and can be leveraged for immune monitoring. DOI: http://dx.doi.org/10.7554/eLife.01944.001.
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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 OpenQuestion graph.