ArticleBlood2012
Basis of CTLA-4 function in regulatory and conventional CD4(+) T cells.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 2 of them syntheses 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
144 citing papers in PubMed, 2 syntheses or guidelines pooled it, 246 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Clinicopathologic and prognostic significance of regulatory T cells in patients with hepatocellular carcinoma: a meta-analysis.Oncotarget · 2017Pooled it
- Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis.Clinical and experimental immunology · 2020Trial
- Phase II study of idelalisib, a selective inhibitor of PI3Kδ, for relapsed/refractory classical Hodgkin lymphoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- First Comprehensive Analysis of Full-Length and Δ2 Foxp3 Isoforms Distribution in PBMCs from Healthy Volunteers.Biomolecules · 2026Article
- Compensatory relationships determine the impact of TGF-β on the humoral immune response to hepatitis B surface antigen.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Review
- Precision Immunotherapeutics for Glioblastoma: Current Approaches and Emerging Strategies in 2026.Cells · 2026Review
- Beyond FoxP3-Identification of a Chicken Regulatory T Cell Signature.European journal of immunology · 2025Article
- Sucralose Consumption Ablates Cancer Immunotherapy Response through Microbiome Disruption.Cancer discovery · 2025Article
- Dissection of the trans-endocytosis and signal inhibition functions of CTLA-4 through the study of a disease-associated Y139C mutation.Cellular & molecular immunology · 2025Article
- Neuropilin-2 functions as a coinhibitory receptor to regulate antigen-induced inflammation and allograft rejection.The Journal of clinical investigation · 2025Article
- Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants.Med (New York, N.Y.) · 2025Article
- Longitudinal single cell profiling of epitope specific memory CD4+ T cell responses to recombinant zoster vaccine.Nature communications · 2025Article
- Molecular biology of the novel anticancer medications: a focus on kinases inhibitors, biologics and CAR T-cell therapy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function.BMC medical genomics · 2025Article
- Revisiting Tregs in cancer and beyond: immunological control and therapeutic potential.Frontiers in immunology · 2025Review
- The tumor immune microenvironment: implications for cancer immunotherapy, treatment strategies, and monitoring approaches.Frontiers in immunology · 2025Review
- Targeted Demethylation of FOXP3-TSDR Enhances the Suppressive Capacity of STAT6-deficient Inducible T Regulatory Cells.Inflammation · 2024Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
CTLA-4 proteins contribute to the suppressor function of regulatory T cells (Tregs), but the mechanism by which they do so remains incompletely understood. In the present study, we assessed CTLA-4 protein function in both Tregs and conventional (Tconv) CD4(+) T cells. We report that CTLA-4 proteins are responsible for all 3 characteristic Treg functions of suppression, TCR hyposignaling, and anergy. However, Treg suppression and anergy only required the external domain of CTLA-4, whereas TCR hyposignaling required its internal domain. Surprisingly, TCR hyposignaling was neither required for Treg suppression nor anergy because costimulatory blockade by the external domain of CTLA-4 was sufficient for both functions. We also report that CTLA-4 proteins were localized in Tregs in submembrane vesicles that rapidly recycled to/from the cell surface, whereas CTLA-4 proteins in naive Tconv cells were retained in Golgi vesicles away from the cell membrane and had no effect on Tconv cell function. However, TCR signaling of Tconv cells released CTLA-4 proteins from Golgi retention and caused activated Tconv cells to acquire suppressor function. Therefore, the results of this study demonstrate the importance of intracellular localization for CTLA-4 protein function and reveal that CTLA-4 protein externalization imparts suppressor function to both regulatory and conventional CD4(+) T cells.
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Identifiers
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.