ArticleProceedings of the National Academy of Sciences of the United States of America2007
Induction of autoimmune disease in CTLA-4-/- mice depends on a specific CD28 motif that is required for in vivo costimulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 90 citations in OpenAlex.
- Immune Checkpoint Inhibitor-Associated Inflammatory Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Review
- A CARMIL2 gain-of-function mutation suffices to trigger most CD28 costimulatory functions in vivo.The Journal of experimental medicine · 2025Article
- Immune Checkpoint Inhibitor-Associated Cutaneous Adverse Events: Mechanisms of Occurrence.International journal of molecular sciences · 2024Review
- Article
- Review
- Pulmonary toxicity of immune checkpoint immunotherapy.The Journal of clinical investigation · 2024Review
- CTLA4 depletes T cell endogenous and trogocytosed B7 ligands via cis-endocytosis.The Journal of experimental medicine · 2023Article
- Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) as an undetermined tool in tumor cells.Human cell · 2023Review
- Head and Neck Cancer Immunotherapy: Molecular Biological Aspects of Preclinical and Clinical Research.Cancers · 2023Review
- Current understanding of CTLA-4: from mechanism to autoimmune diseases.Frontiers in immunology · 2023Review
- In Vitro Analysis of CTLA-4-Mediated Transendocytosis by Regulatory T Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Genetics of Immune Dysregulation and Cancer Predisposition: Two Sides of the Same Coin.Clinical and experimental immunology · 2022Review
- Transcriptomic signatures associated with autoimmune thyroiditis in papillary thyroid carcinoma and cancer immunotherapy-induced thyroid dysfunction.Computational and structural biotechnology journal · 2022Article
- Pathogenesis of Autoimmune Hepatitis-Cellular and Molecular Mechanisms.International journal of molecular sciences · 2021Review
- Targeting the spectrum of immune checkpoints in prostate cancer.Expert review of clinical pharmacology · 2021Review
- Genomic profiling of T-cell activation suggests increased sensitivity of memory T cells to CD28 costimulation.Genes and immunity · 2020Article
- A guide to cancer immunotherapy: from T cell basic science to clinical practice.Nature reviews. Immunology · 2020Review
- Scientifically based combination therapies with immuno-oncology checkpoint inhibitors.British journal of clinical pharmacology · 2020Review
- Safety and efficacy of abatacept in patients with treatment-resistant SARCoidosis (ABASARC) - protocol for a multi-center, single-arm phase IIa trial.Contemporary clinical trials communications · 2020Article
- T cell costimulation, checkpoint inhibitors and anti-tumor therapy.Journal of biosciences · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
CTLA-4-deficient mice develop a lethal autoimmune lymphoproliferative disorder that is strictly dependent on in vivo CD28 costimulation. Nevertheless, it is not known whether there is a specific site on the CD28 molecule that is required for induction of autoimmunity. Using CTLA-4-deficient mice expressing CD28 molecules with various point mutations in the CD28 cytosolic tail, the present study documents that in vivo costimulation for induction of autoimmune disease strictly requires an intact C-terminal proline motif that promotes lymphocyte-specific protein tyrosine kinase Lck binding to the CD28 cytosolic tail, because point mutations in C-terminal proline residues (Pro-187 and Pro-190) completely prevented disease induction. In contrast, in vivo costimulation for disease induction did not require either an intact YMNM motif or an intact N-terminal proline motif, which, respectively, promote phosphoinositide 3-kinase and IL2-inducible T cell kinase binding to the CD28 cytosolic tail. Thus, in vivo CD28 costimulation for induction of autoimmune disease is strictly and specifically dependent on an intact C-terminal proline motif that serves as a lymphocyte-specific protein tyrosine Lck kinase binding site in the CD28 cytosolic tail.
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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.