ArticleProceedings of the National Academy of Sciences of the United States of America2000
Pinpointing when T cell costimulatory receptor CTLA-4 must be engaged to dampen diabetogenic T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed, 100 citations in OpenAlex.
- Preclinical mouse models of immune checkpoint inhibitor-associated myocarditis.Nature cardiovascular research · 2025Review
- Toxicity in the era of immune checkpoint inhibitor therapy.Frontiers in immunology · 2024Review
- MERTK on mononuclear phagocytes regulates T cell antigen recognition at autoimmune and tumor sites.The Journal of experimental medicine · 2021Article
- Inhibitory receptor agonists: the future of autoimmune disease therapeutics?Current opinion in immunology · 2020Review
- Type 1 diabetes pathogenesis and the role of inhibitory receptors in islet tolerance.Annals of the New York Academy of Sciences · 2020Review
- Serum sCTLA-4 levels and clinical manifestations in ankylosing spondylitis patients.European journal of rheumatology · 2018Article
- CTLA-4 expressed by FOXP3Immunology · 2017Article
- Immunometabolic Regulations Mediated by Coinhibitory Receptors and Their Impact on T Cell Immune Responses.Frontiers in immunology · 2017Review
- Type 1 Diabetes: A Chronic Anti-Self-Inflammatory Response.Frontiers in immunology · 2017Review
- Co-stimulatory and Co-inhibitory Pathways in Autoimmunity.Immunity · 2016Review
- GM-CSF-neuroantigen fusion proteins reverse experimental autoimmune encephalomyelitis and mediate tolerogenic activity in adjuvant-primed environments: association with inflammation-dependent, inhibitory antigen presentation.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Treg and CTLA-4: two intertwining pathways to immune tolerance.Journal of autoimmunity · 2013Review
- At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy.Journal of leukocyte biology · 2013Review
- Accelerated type 1 diabetes induction in mice by adoptive transfer of diabetogenic CD4+ T cells.Journal of visualized experiments : JoVE · 2013Article
- The B7-independent isoform of CTLA-4 functions to regulate autoimmune diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Breakdown in peripheral tolerance in type 1 diabetes in mice and humans.Cold Spring Harbor perspectives in medicine · 2012Review
- Preventive treatment with methylprednisolone paradoxically exacerbates experimental autoimmune encephalomyelitis.International journal of endocrinology · 2012Article
- Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family.Immunological reviews · 2011Review
- Use of nonobese diabetic mice to understand human type 1 diabetes.Endocrinology and metabolism clinics of North America · 2010Review
- Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.Nature immunology · 2009Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engagement of the T cell costimulatory receptor CTLA-4 can potently down-regulate an immune response. For example, in a T cell receptor transgenic mouse model of autoimmune diabetes, CTLA-4 interactions keep pancreatic islet-reactive T cells in check, evidenced by the finding that mAb blockade of CTLA-4 rapidly provokes diabetes in animals that would not normally succumb until many months later. Interestingly, this effect is only observed early in the course of disease, before insulitis is stably entrenched. Here, we have exploited a highly synchronous and easily manipulable transfer system to determine precisely when CTLA-4 must be engaged to check the diabetogenicity of islet-reactive T cells. Our results indicate that CTLA-4 interactions during initial priming of the T cells in the pancreatic lymph nodes are not determinant. Rather, the critical interactions occur when the T cells secondarily reencounter their antigen in the target organ, the pancreatic islets. In addition, we made use of CTLA-4-deficient mice to bolster our interpretation that CTLA-4 engagement has a dampening rather than an enhancing influence on diabetes progression.
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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.