ArticleThe Journal of biological chemistry2012
Ligation of cytotoxic T lymphocyte antigen-4 to T cell receptor inhibits T cell activation and directs differentiation into Foxp3+ regulatory T cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Regulatory T cell therapy in solid organ transplantation: clinical applications and laboratory monitoring strategies.Clinical transplantation and research · 2025Review
- Structure-guided bispecific antibody engineering confers broad protection against KP.3.1.1 and sarbecoviruses.iScience · 2025Article
- Oxidative Stress Promotes Instability of Regulatory T Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.Frontiers in immunology · 2021Article
- Immunotherapy for HER2-positive breast cancer: recent advances and combination therapeutic approaches.Breast cancer (Dove Medical Press) · 2019Review
- Enhanced Suppressive Activity of Regulatory T Cells in the Microenvironment of Malignant Pleural Effusions.Journal of immunology research · 2018Article
- Checkpoint inhibitors in lung cancer: latest developments and clinical potential.Therapeutic advances in medical oncology · 2016Review
- Article
- The environment of regulatory T cell biology: cytokines, metabolites, and the microbiome.Frontiers in immunology · 2015Review
- Victory and defeat in the induction of a therapeutic response through vaccine therapy for human and canine brain tumors: a review of the state of the art.Critical reviews in immunology · 2014Review
- Inhibitory effects of belatacept on allospecific regulatory T-cell generation in humans.Transplantation · 2013Article
- Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.Cancer research · 2013Article
- mTOR and lymphocyte metabolism.Current opinion in immunology · 2013Review
- A bispecific protein capable of engaging CTLA-4 and MHCII protects non-obese diabetic mice from autoimmune diabetes.PloS one · 2013Article
- Role of cytokines in thymus- versus peripherally derived-regulatory T cell differentiation and function.Frontiers in immunology · 2013Article
- ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells.BMC genomics · 2012Article
- Review
- Innate and adaptive immune responses in asthma.Nature medicine · 2012Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cross-linking of ligand-engaged cytotoxic T lymphocyte antigen-4 (CTLA-4) to the T cell receptor (TCR) during the early phase of T cell activation attenuates TCR signaling, leading to T cell inhibition. To promote this event, a bispecific fusion protein comprising a mutant mouse CD80 (CD80w88a) and lymphocyte activation antigen-3 was engineered to concurrently engage CTLA-4 and cross-link it to the TCR. Cross-linking is expected to be attained via ligation of CTLA-4 first to MHCII and then indirectly to the TCR, generating a CTLA-4-MHCII-TCR trimolecular complex that forms between T cells and antigen-presenting cells during T cell activation. Treating T cells with this bispecific fusion protein inhibited T cell activation. In addition, it induced the production of IL-10 and TGF-β and attenuated AKT and mTOR signaling. Intriguingly, treatment with the bispecific fusion protein also directed early T cell differentiation into Foxp3-positive regulatory T cells (Tregs). This process was dependent on the endogenous production of TGF-β. Thus, bispecific fusion proteins that engage CTLA-4 and co-ligate it to the TCR during the early phase of T cell activation can negatively regulate the T cell response. Bispecific biologics with such dual functions may therefore represent a novel class of therapeutics for immune modulation. These findings presented here also reveal a potential new role for CTLA-4 in Treg differentiation.
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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.