ArticleProceedings of the National Academy of Sciences of the United States of America2016
Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 229 citations in OpenAlex.
- Association betweenAging · 2021Pooled it
- Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation.The Journal of allergy and clinical immunology · 2018Trial
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- Therapeutic exploration of combined local hyperthermia and anti-CD200 blockade therapy in the EMT6 breast cancer model.Medical oncology (Northwood, London, England) · 2026Article
- Understanding immune checkpoint inhibitors-related myocarditis: Mechanisms and targeted therapeutic pathways.Theranostics · 2026Review
- Guarding the heart in the era of immunotherapies: insights for cardio-oncology practice.Frontiers in pharmacology · 2026Review
- Near Infrared Photoimmunotherapy for Lung Cancer: Recent Development and Perspective.ImmunoTargets and therapy · 2026Review
- A review of immune checkpoint inhibitor-associated myocarditis: Epidemiology, pathogenesis, and biomarkers.Human vaccines & immunotherapeutics · 2025Review
- Immune checkpoint inhibitor-related arthritis and oral disorders: shared pathophysiology and clinical implications for rheumatology and oral health.Cancer cell international · 2025Review
- The co-inhibitory receptor TIGIT promotes tissue-protective functions in T cells.Nature immunology · 2025Article
- CTLA-4-Ig therapy preserves cardiac function following myocardial infarction with reperfusion.Cardiovascular research · 2025Article
- Immune Checkpoint Inhibitor-Induced Diabetes Mellitus-A Brief Review and Three Case Reports.Journal of clinical medicine · 2025Review
- Circulating Plasma Proteins as Biomarkers for Immunotherapy Toxicity: Insights from Proteome-Wide Mendelian Randomization and Bioinformatics Analysis.Biomedicines · 2025Article
- CTLA-4 expression on tregs is needed for suppression of autoimmune uveitis.Scientific reports · 2025Article
- Article
- Preclinical mouse models of immune checkpoint inhibitor-associated myocarditis.Nature cardiovascular research · 2025Review
82 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
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is essential for immunological (self-) tolerance, but due to the early fatality of CTLA-4 KO mice, its specific function in central and peripheral tolerance and in different systemic diseases remains to be determined. Here, we further examined the role of CTLA-4 by abrogating CTLA-4 expression in adult mice and compared the resulting autoimmunity that follows with that produced by congenital CTLA-4 deficiency. We found that conditional deletion of CTLA-4 in adult mice resulted in spontaneous lymphoproliferation, hypergammaglobulinemia, and histologically evident pneumonitis, gastritis, insulitis, and sialadenitis, accompanied by organ-specific autoantibodies. However, in contrast to congenital deficiency, this was not fatal. CTLA-4 deletion induced preferential expansion of CD4(+)Foxp3(+) Treg cells. However, T cells from CTLA-4-deficient inducible KO mice were able to adoptively transfer the diseases into T cell-deficient mice. Notably, cell transfer of thymocytes de novo produced myocarditis, otherwise not observed in donor mice depleted in adulthood. Moreover, CTLA-4 deletion in adult mice had opposing impacts on induced autoimmune models. Thus, although CTLA-4-deficient mice had more severe collagen-induced arthritis (CIA), they were protected against peptide-induced experimental autoimmune encephalomyelitis (EAE); however, onset of protein-induced EAE was only delayed. Collectively, this indicates that CTLA-4 deficiency affects both central and peripheral tolerance and Treg cell-mediated suppression.
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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.