ArticleThe Journal of experimental medicine2015
Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.
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Who cites it
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Abatacept Targets T Follicular Helper and Regulatory T Cells, Disrupting Molecular Pathways That Regulate Their Proliferation and Maintenance.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- A homozygous CTLA-4 variant causes CTLA-4 deficiency with severe immune dysregulation.Journal of human immunity · 2026Article
- IL-6-induced C/EBPα drives follicular regulatory T cell differentiation to regulate humoral immunity in mice.Nature communications · 2026Article
- Activation and lineage specific Lag3 expression dynamics in T cells.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Near Infrared Photoimmunotherapy for Lung Cancer: Recent Development and Perspective.ImmunoTargets and therapy · 2026Review
- The role of coinhibitory receptor-expressing non-T cells in inflammation and immunity: unsung heroes or peripheral players?Experimental & molecular medicine · 2025Review
- CTLA-4 expression on tregs is needed for suppression of autoimmune uveitis.Scientific reports · 2025Article
- Treg Control of CD80/CD86 Expression Mediates Immune System Homeostasis.European journal of immunology · 2025Article
- Role of Regulatory T Cells in Pulmonary Ageing and COPD Development.International journal of molecular sciences · 2025Review
- The role of immunotherapy in targeting tumor microenvironment in genitourinary cancers.Frontiers in immunology · 2025Review
- Interacting roles of gut microbiota and T cells in the development of autoimmune hepatitis.Frontiers in immunology · 2025Review
- Immunometabolism of Tregs: mechanisms, adaptability, and therapeutic implications in diseases.Frontiers in immunology · 2025Review
- Regulatory T cells in inflamed liver are dysfunctional in murine primary biliary cholangitis.Clinical and experimental immunology · 2024Article
- Review
- Anti-CTLA-4 nanobody as a promising approach in cancer immunotherapy.Cell death & disease · 2024Review
- Regulation of Treg cells by cytokine signaling and co-stimulatory molecules.Frontiers in immunology · 2024Review
- CTLA-4 Checkpoint Inhibition Improves Sepsis Survival in Alcohol-Exposed Mice.ImmunoHorizons · 2024Article
- X-CHIME enables combinatorial, inducible, lineage-specific and sequential knockout of genes in the immune system.Nature immunology · 2024Article
- Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.Cell communication and signaling : CCS · 2023Review
71 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during adulthood does not precipitate systemic autoimmunity, but surprisingly confers protection from experimental autoimmune encephalomyelitis (EAE) and does not lead to increased resistance to MC38 tumors. Deletion of Ctla4 during adulthood was accompanied by activation and expansion of both conventional CD4(+)Foxp3(-) (T conv) and regulatory Foxp3(+) (T reg cells) T cell subsets; however, deletion of CTLA-4 on T reg cells was necessary and sufficient for protection from EAE. CTLA-4 deleted T reg cells remained functionally suppressive. Deletion of Ctla4 on T reg cells alone or on all adult T cells led to major changes in the Ctla4 sufficient T conv cell compartment, including up-regulation of immunoinhibitory molecules IL-10, LAG-3 and PD-1, thereby providing a compensatory immunosuppressive mechanism. Collectively, our findings point to a profound role for CTLA-4 on T reg cells in limiting their peripheral expansion and activation, thereby regulating the phenotype and function of T conv cells.
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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.