ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Regulatory T cells require TCR signaling for their suppressive function.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 56 citations in OpenAlex.
- Isolation of Pure Stable Human Treg Cells Based on Expression of GPA33.European journal of immunology · 2026Article
- Endothelium-Treg Communication Through Extracellular Vesicle Transfer Exacerbates Acute Respiratory Distress Syndrome.Journal of extracellular vesicles · 2026Article
- Association ofFrontiers in bioinformatics · 2026Article
- The relativity of regulatory T cell suppression modes.Frontiers in immunology · 2026Review
- Blimp-1 benefits gut-homing regulatory T cells by maintaining migration/suppressive function in autoimmune diabetes-prone mice.EBioMedicine · 2025Article
- Dynamic Foxp3-chromatin interaction controls tunable Treg cell function.The Journal of experimental medicine · 2024Article
- Deciphering the developmental trajectory of tissue-resident Foxp3Frontiers in immunology · 2024Review
- Clinical Manufacturing of Regulatory T Cell Products For Adoptive Cell Therapy and Strategies to Improve Therapeutic Efficacy.Organogenesis · 2023Review
- Role of Regulatory T Cells and Their Potential Therapeutic Applications in Celiac Disease.International journal of molecular sciences · 2023Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Immunosuppressive Signaling Pathways as Targeted Cancer Therapies.Biomedicines · 2022Review
- CD3e-immunotoxin spares CD62LFrontiers in immunology · 2022Article
- T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2021Review
- CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.Nature communications · 2021Article
- Strength and Numbers: The Role of Affinity and Avidity in the 'Quality' of T Cell Tolerance.Cells · 2021Review
- Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy.Frontiers in immunology · 2021Review
- Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.European journal of immunology · 2020Article
- Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo.eLife · 2020Article
- Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development.The Journal of pathology · 2020Article
- Multifaceted effects of soluble human CD6 in experimental cancer models.Journal for immunotherapy of cancer · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Regulatory T cells (Tregs) are a subset of CD4(+) T cells that maintain immune tolerance in part by their ability to inhibit the proliferation of conventional CD4(+) T cells (Tconvs). The role of the TCR and the downstream signaling pathways required for this suppressive function of Tregs are not fully understood. To yield insight into how TCR-mediated signals influence Treg suppressive function, we assessed the ability of Tregs with altered TCR-mediated signaling capacity to inhibit Tconv proliferation. Mature Tregs deficient in Src homology 2 domain containing leukocyte protein of 76 kDa (SLP-76), an adaptor protein that nucleates the proximal signaling complex downstream of the TCR, were unable to inhibit Tconv proliferation, suggesting that TCR signaling is required for Treg suppressive function. Moreover, Tregs with defective phospholipase C γ (PLCγ) activation due to a Y145F mutation of SLP-76 were also defective in their suppressive function. Conversely, enhancement of diacylglycerol-mediated signaling downstream of PLCγ by genetic ablation of a negative regulator of diacylglycerol kinase ζ increased the suppressive ability of Tregs. Because SLP-76 is also important for integrin activation and signaling, we tested the role of integrin activation in Treg-mediated suppression. Tregs lacking the adaptor proteins adhesion and degranulation promoting adapter protein or CT10 regulator of kinase/CT10 regulator of kinase-like, which are required for TCR-mediated integrin activation, inhibited Tconv proliferation to a similar extent as wild-type Tregs. Together, these data suggest that TCR-mediated PLCγ activation, but not integrin activation, is required for Tregs to inhibit Tconv proliferation.
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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.