ArticleCell2021
A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells.
Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Risk of flare or relapse in patients with immune-mediated diseases following SARS-CoV-2 vaccination: a systematic review and meta-analysis.European journal of medical research · 2024Pooled it
- Receptor-tethered orthogonal IL-2 enhances regulatory T cell therapy.The Journal of experimental medicine · 2026Article
- Impact of Chronic Infection-Induced Inflammation on TREG Cell Homeostasis.European journal of immunology · 2026Article
- TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro.Cellular & molecular immunology · 2026Article
- Decoding cellular population dynamics through mechanistic modelling and statistical data analysis.NPJ systems biology and applications · 2026Review
- T Cell Receptor Repertoires Across the Continuum of Vascular, Myocardial, and Age-Related Diseases.Immunological reviews · 2026Review
- Asymmetry and redundancy of STAT5 paralogs across CD8Communications biology · 2026Article
- Immune checkpoints in a genetically engineered mouse model of spontaneous autoimmune uveitis.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Spontaneous organ-specific eye autoimmune disease resulting from two engineered gene mutations compromising immune tolerance.Frontiers in immunology · 2026Review
- Dendritic Cell Organization and Function in Innate and Adaptive Immune Defense Within Lymph Nodes.Immunological reviews · 2026Review
- The relativity of regulatory T cell suppression modes.Frontiers in immunology · 2026Review
- T cell decision-making decodes the dynamic antigenic landscape.Frontiers in immunology · 2026Review
- Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.Oncoimmunology · 2025Review
- Dynamics and variegation in the Treg response to Interleukin-2.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Bridging single cells to organs: Mesoscale modules as fundamental units of tissue function.Cell · 2025Review
- Functional Specialization and Collaboration of cDC2 Subsets in CD4+ T Cell Priming and Differentiation.Immunological reviews · 2025Review
- Genistein enhances anti-PD-1 efficacy in melanoma by suppressing regulatory T cell differentiation and activity.Scientific reports · 2025Article
- Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Cellular Adaptation to Mechanical Stress Emerges via Cell Shrinkage Triggered by Nonlinear Calcium Elevation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
A fraction of mature T cells can be activated by peripheral self-antigens, potentially eliciting host autoimmunity. We investigated homeostatic control of self-activated T cells within unperturbed tissue environments by combining high-resolution multiplexed and volumetric imaging with computational modeling. In lymph nodes, self-activated T cells produced interleukin (IL)-2, which enhanced local regulatory T cell (Treg) proliferation and inhibitory functionality. The resulting micro-domains reciprocally constrained inputs required for damaging effector responses, including CD28 co-stimulation and IL-2 signaling, constituting a negative feedback circuit. Due to these local constraints, self-activated T cells underwent transient clonal expansion, followed by rapid death ("pruning"). Computational simulations and experimental manipulations revealed the feedback machinery's quantitative limits: modest reductions in Treg micro-domain density or functionality produced non-linear breakdowns in control, enabling self-activated T cells to subvert pruning. This fine-tuned, paracrine feedback process not only enforces immune homeostasis but also establishes a sharp boundary between autoimmune and host-protective T cell responses.
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What OpenQuestion holds
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.