ArticleProceedings of the National Academy of Sciences of the United States of America1997
Thymocyte development is normal in CTLA-4-deficient mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 147 citations in OpenAlex.
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- Case Report: Aplastic anemia related to a novelFrontiers in pediatrics · 2024Article
- Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors.Biology · 2023Review
- 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
- Mechanisms of immunogenic cell death and immune checkpoint blockade therapy.The Kaohsiung journal of medical sciences · 2021Review
- CTLA-4 in Regulatory T Cells for Cancer Immunotherapy.Cancers · 2021Review
- A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitor-Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention.Cancer discovery · 2021Article
- IL36 Cooperates With Anti-CTLA-4 mAbs to Facilitate Antitumor Immune Responses.Frontiers in immunology · 2020Article
- Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease.Physiological reviews · 2019Review
- Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States.Immunity · 2019Article
- Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity.JCI insight · 2017Article
- Immune Toxicities Elicted by CTLA-4 Blockade in Cancer Patients Are Associated with Early Diversification of the T-cell Repertoire.Cancer research · 2017Article
- Basics of PD-1 in self-tolerance, infection, and cancer immunity.International journal of clinical oncology · 2016Review
- 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
- Article
- Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity.The Journal of experimental medicine · 2015Article
- Selective Treg reconstitution during lymphopenia normalizes DC costimulation and prevents graft-versus-host disease.The Journal of clinical investigation · 2015Article
- Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma.Clinical, cosmetic and investigational dermatology · 2013Review
- At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy.Journal of leukocyte biology · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Recent studies indicate that CTLA-4 interaction with B7 ligands transduces an inhibitory signal to T lymphocytes. Mice homozygous for a null mutation in CTLA-4 have provided the most dramatic example of the functional importance of CTLA-4 in vivo. These animals develop a fatal lymphoproliferative disorder and were reported to have an increase in CD4(+) and CD8(+) thymocytes and CD4(-)CD8(-) thymocytes, and a decrease in CD4(+)CD8(+) thymocytes. Based on these observations, it was proposed that CTLA-4 is necessary for normal thymocyte development. In this study, CTLA-4-deficient mice carrying an insertional mutation into exon 3 of the ctla-4 gene were generated. Although these mice display a lymphoproliferative disorder similar to previous reports, there was no alteration in the thymocyte profiles when the parathymic lymph nodes were excluded from the thymi. Further, thymocyte development was normal throughout ontogeny and in neonates, and there was no increase in thymocyte production. Finally, T cell antigen receptor signaling, as assessed by proximal and distal events, was not altered in thymocytes from CTLA-4(-/-) animals. Collectively, these results clearly demonstrate that the abnormal T cell expansion in the CTLA-4-deficient mice is not due to altered thymocyte development and suggest that the apparent altered thymic phenotype previously described was due to the inclusion of parathymic lymph nodes and, in visibly ill animals, to the infiltration of the thymus by activated peripheral T cells. Thus it appears that CTLA-4 is primarily involved in the regulation of peripheral T cell activation.
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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.