ArticleThe Journal of experimental medicine2009
CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 151 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
151 citing papers in PubMed, 3 syntheses or guidelines pooled it, 256 citations in OpenAlex.
- Systemic treatment of immune checkpoint inhibitor-induced psoriasis: Inference-based guidance.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Pooled it
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- CTLA-4 +49 G/A, a functional T1D risk SNP, affects CTLA-4 level in Treg subsets and IA-2A positivity, but not beta-cell function.Scientific reports · 2018Pooled it
- Immune checkpoint inhibitor-induced cardiotoxicity: from immune mechanisms to clinical surveillance and targeted therapies.Frontiers in cardiovascular medicine · 2026Review
- A review of immune checkpoint inhibitor-associated myocarditis: Epidemiology, pathogenesis, and biomarkers.Human vaccines & immunotherapeutics · 2025Review
- Sucralose Consumption Ablates Cancer Immunotherapy Response through Microbiome Disruption.Cancer discovery · 2025Article
- Beyond monotherapy: multimodal strategies integrating immune checkpoint inhibitors in lymphoma management.Frontiers in immunology · 2025Review
- Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis.JID innovations : skin science from molecules to population health · 2025Article
- Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8Cancer cell · 2024Article
- Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations.Cancers · 2024Review
- Epigenetic reprogramming of T cells: unlocking new avenues for cancer immunotherapy.Cancer metastasis reviews · 2024Review
- Modulatory Role of Phytochemicals/Natural Products in Cancer Immunotherapy.Current medicinal chemistry · 2024Review
- Regulatory T cells in lung disease and transplantation.Bioscience reports · 2023Review
- Both intratumoral regulatory T cell depletion and CTLA-4 antagonism are required for maximum efficacy of anti-CTLA-4 antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Crosstalk of Immune Cells and Platelets in an Ovarian Cancer Microenvironment and Their Prognostic Significance.International journal of molecular sciences · 2023Review
- Review
- Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice.Cellular immunology · 2023Article
- [Development of autoimmunity in patients with primary immunodeficiencies].Revista medica del Instituto Mexicano del Seguro Social · 2023Article
- Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors.Biology · 2023Review
- Mechanisms underlying response and resistance to immune checkpoint blockade in cancer immunotherapy.Frontiers in oncology · 2023Review
91 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3(+) regulatory T cells. CTLA-4-deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4-deficient and -sufficient bone marrow (BM)-derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4(-/-) T cells in trans by CTLA-4-sufficient T cells is a reversible process that requires the persistent presence of FOXP3(+) regulatory T cells with a diverse TCR repertoire. Based on gene expression studies, the regulatory T cells do not appear to act directly on T cells, suggesting they may instead modulate the stimulatory activities of antigen-presenting cells. These results demonstrate that CTLA-4 is absolutely required for FOXP3(+) regulatory T cell function in vivo.
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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.