ArticleProceedings of the National Academy of Sciences of the United States of America2013
CTLA-4 controls the thymic development of both conventional and regulatory T cells through modulation of the TCR repertoire.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- CTLA-4-two pathways to anti-tumour immunity?Immunotherapy advances · 2025Review
- Association between Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4) Locus and Early-Onset Anti-acetylcholine Receptor-Positive Myasthenia Gravis in Serbian Patients.Molecular neurobiology · 2024Article
- The type 1 diabetes susceptibility locusFrontiers in immunology · 2024Article
- Turning up the heat: CTLA4 blockade in urothelial cancer.Nature reviews. Urology · 2024Review
- Article
- Negative times negative equals positive, THEMIS sets the rule on thymic selection and peripheral T cell responses.Biomedical journal · 2022Review
- Blockade of novel immune checkpoints and new therapeutic combinations to boost antitumor immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- Ectopic FOXP3 Expression in Combination with TGF-β1 and IL-2 Stimulation Generates Limited Suppressive Function in Human Primary Activated Thymocytes Ex Vivo.Biomedicines · 2021Article
- Tumor-infiltrating CD8Drug discovery today · 2021Review
- Thymus and autoimmunity.Seminars in immunopathology · 2021Review
- Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion.Frontiers in immunology · 2021Article
- Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.Pharmaceutics · 2020Review
- Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States.Immunity · 2019Article
- Immune Dysfunction in Non-Hodgkin Lymphoma: Avenues for New Immunotherapy-Based Strategies.Current hematologic malignancy reports · 2017Review
- Next-Generation Sequencing Reveals Restriction and Clonotypic Expansion of Treg Cells in Juvenile Idiopathic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- Progress and challenges for treating Type 1 diabetes.Journal of autoimmunity · 2016Review
- Co-stimulatory and Co-inhibitory Pathways in Autoimmunity.Immunity · 2016Review
- Dysregulation of peritoneal cavity B1a cells and murine primary biliary cholangitis.Oncotarget · 2016Article
- Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is of pivotal importance for self-tolerance, with deficiency or unfavorable polymorphisms leading to autoimmune disease. Tolerance to self-antigens is achieved through thymic deletion of highly autoreactive conventional T (Tconv) cells and generation of FoxP3(+) regulatory T (Treg) cells. The main costimulatory molecule, CD28, augments the negative selection of Tconv cells and promotes the generation of FoxP3(+) Treg cells. The role of its antagonistic homolog CTLA-4, however, remains a topic of debate. To address this topic, we investigated the thymic development of T cells in the presence and absence of CTLA-4 in a T-cell receptor (TCR) transgenic mouse model specific for the myelin basic protein peptide Ac1-9. We reveal that CTLA-4 is expressed in the corticomedullary region of the thymus. Its absence alters the response of CD4(+)CD8(-) thymocytes to self-antigen recognition, which affects the quantity of the Treg cells generated and broadens the repertoire of peripheral Tconv cells. T-cell repertoire alteration after deletion of CTLA-4 results from changes in TCR Vα and Jα segment selection as well as CDR3α composition in Tconv and Treg cells. CTLA-4, therefore, regulates the early development of self-reactive T cells in the thymus and plays a key role in central tolerance.
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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.