ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Cutting edge: cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review.Cell communication and signaling : CCS · 2021Pooled it
- Review
- Immune checkpoint inhibitor-induced cardiotoxicity: from immune mechanisms to clinical surveillance and targeted therapies.Frontiers in cardiovascular medicine · 2026Review
- Dermatotoxicity of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: Current Advances in Mechanistic Insights and Predictive Biomarker Identification.Cancer management and research · 2025Review
- Spectrum of Treg and self-reactive T cells: single cell perspectives from old friend HTLV-1.Discovery immunology · 2024Review
- Turning up the heat: CTLA4 blockade in urothelial cancer.Nature reviews. Urology · 2024Review
- Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors.Frontiers in immunology · 2023Review
- In Vitro Analysis of CTLA-4-Mediated Transendocytosis by Regulatory T Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Therapeutic gene editing of T cells to correct CTLA-4 insufficiency.Science translational medicine · 2022Article
- Selective CD28 blockade impacts T cell differentiation during homeostatic reconstitution following lymphodepletion.Frontiers in immunology · 2022Article
- Cytotoxic T lymphocyte antigen-4 regulates development of xenogenic graft versus host disease in mice via modulation of host immune responses induced by changes in human T cell engraftment and gene expression.Clinical and experimental immunology · 2021Article
- Regulation of the innate immune cells during pregnancy: An immune checkpoint perspective.Journal of cellular and molecular medicine · 2021Review
- Article
- CD86 Is a Selective CD28 Ligand Supporting FoxP3+ Regulatory T Cell Homeostasis in the Presence of High Levels of CTLA-4.Frontiers in immunology · 2020Article
- Vitamin D Increases CTLA-4 Gene Expression in Patients with Mild to Moderate Ulcerative Colitis.Middle East journal of digestive diseases · 2019Article
- Impact of selective CD28 blockade on virus-specific immunity to a murine Epstein-Barr virus homolog.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- CTLA-4 antibody ipilimumab negatively affects CD4Cancer immunology, immunotherapy : CII · 2019Article
- Tipping the balance: inhibitory checkpoints in intestinal homeostasis.Mucosal immunology · 2019Review
- MALT1-Deficient Mice Develop Atopic-Like Dermatitis Upon Aging.Frontiers in immunology · 2019Article
- MALT1 Proteolytic Activity Suppresses Autoimmunity in a T Cell Intrinsic Manner.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The CTLA-4 pathway is a key regulator of T cell activation and a critical failsafe against autoimmunity. Although early models postulated that CTLA-4 transduced a negative signal, in vivo evidence suggests that CTLA-4 functions in a cell-extrinsic manner. That multiple cell-intrinsic mechanisms have been attributed to CTLA-4, yet its function in vivo appears to be cell-extrinsic, has been an ongoing paradox in the field. Although CTLA-4 expressed on conventional T cells (Tconv) can mediate inhibitory function, it is unclear why this fails to manifest as an intrinsic effect. In this study, we show that Tconv-expressed CTLA-4 can function in a cell-extrinsic manner in vivo. CTLA-4(+/+) T cells, from DO11/rag(-/-) mice that lack regulatory T cells, were able to regulate the response of CTLA-4(-/-) T cells in cotransfer experiments. This observation provides a potential resolution to the above paradox and suggests CTLA-4 function on both Tconv and regulatory T cells can be achieved through cell-extrinsic mechanisms.
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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.