ReviewJournal of autoimmunity2013
Treg and CTLA-4: two intertwining pathways to immune tolerance.
Review in Journal of autoimmunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 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.
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Who cites it
237 citing papers in PubMed, 2 syntheses or guidelines pooled it, 396 citations in OpenAlex.
- Gender-Dependent Specificities in Cutaneous Melanoma Predisposition, Risk Factors, Somatic Mutations, Prognostic and Predictive Factors: A Systematic Review.International journal of environmental research and public health · 2021Pooled 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
- Follicular Helper T Cell Derived Exosomes Promote B Cell Proliferation and Differentiation in Antibody-Mediated Rejection after Renal Transplantation.BioMed research international · 2019Trial
- Review
- Microbiota and immune-related adverse events in cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Taming autoimmunity: Alpha-1 antitrypsin overexpressing mesenchymal stromal cells promote regulatory T cell crosstalk to reverse diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- First-in-human study of intravenous bispecific CTLA-4 × OX40 antibody (ATOR-1015) in advanced solid malignancies.ESMO open · 2026Article
- Evaluation of +49 A>G (rs231775) Variant in CTLA4 Gene and SCTLA-4 Serum Levels in Plaque Psoriasis in a Mestizo Mexican Population.International journal of molecular sciences · 2026Article
- Activation and lineage specific Lag3 expression dynamics in T cells.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Review
- LDRT combined with anti-PD-1 promotes tumor regression in head and neck squamous cell carcinoma through tumor metaprogram evolution and immune cell reprogramming.Journal of experimental & clinical cancer research : CR · 2026Article
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Regulatory T Cell Heterogeneity in the Steady State and Tumor.Immune network · 2026Review
- The double-positive cells in the tumor microenvironment.Journal of translational internal medicine · 2026Article
- CD4Frontiers in immunology · 2026Review
- A stage-based framework to interpret regulatory T cell biology after heart transplantation.Frontiers in cardiovascular medicine · 2026Review
- Tumor microenvironment-induced epigenetic reprogramming of Tregs and its impact on immunotherapy.Frontiers in genetics · 2026Review
- Overcoming resistance to immune checkpoint inhibitor therapy in acute myeloid leukemia.Frontiers in oncology · 2026Review
- Host-response trajectories in necrotizing fasciitis: host-pathogen interactions, immune evasion, and immunoparalysis.Frontiers in cellular and infection microbiology · 2026Review
- Immune Checkpoint Restoration as a Therapeutic Strategy to Halt Diabetes-Driven Atherosclerosis.Biology · 2025Review
177 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
1 author at 1 institution in 1 country.
Funding
Abstract
Both the CTLA-4 pathway and regulatory T cells (Treg) are essential for the control of immune homeostasis. Their therapeutic relevance is highlighted by the increasing use of anti-CTLA-4 antibody in tumor therapy and the development of Treg cell transfer strategies for use in autoimmunity and transplantation settings. The CTLA-4 pathway first came to the attention of the immunological community in 1995 with the discovery that mice deficient in Ctla-4 suffered a fatal lymphoproliferative syndrome. Eight years later, mice lacking the critical Treg transcription factor Foxp3 were shown to exhibit a remarkably similar phenotype. Much of the debate since has centered on the question of whether Treg suppressive function requires CTLA-4. The finding that it does in some settings but not in others has provoked controversy and inevitable polarization of opinion. In this article, I suggest that CTLA-4 and Treg represent complementary and largely overlapping mechanisms of immune tolerance. I argue that Treg commonly use CTLA-4 to effect suppression, however CTLA-4 can also function in the non-Treg compartment while Treg can invoke CTLA-4-independent mechanisms of suppression. The notion that Foxp3 and CTLA-4 direct independent programs of immune regulation, which in practice overlap to a significant extent, will hopefully help move us towards a better appreciation of the underlying biology and therapeutic significance of these pathways.
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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.