ArticleThe Journal of clinical investigation2003
Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3gamma1(Ala-Ala).
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
73 citing papers in PubMed, 177 citations in OpenAlex.
- An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.The New England journal of medicine · 2019Trial
- Trial
- Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.PLoS medicine · 2016Trial
- Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial.Diabetologia · 2013Trial
- Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years.Clinical immunology (Orlando, Fla.) · 2009Trial
- Trial
- Treatment of acute kidney allograft rejection with a non-mitogenic CD3 antibody.Clinical and experimental immunology · 2003Trial
- Trial
- Anti-CD3 mAb treatment reshapes infiltrating T and β cells in the islets in autoimmune diabetes.JCI insight · 2026Article
- Latent EBV enhances the efficacy of anti-CD3 mAb in Type 1 diabetes.Nature communications · 2025Article
- Explainable machine learning for profiling the immunological synapse and functional characterization of therapeutic antibodies.Nature communications · 2023Article
- Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice.Cellular immunology · 2023Article
- Activation pathways that drive CD4Immunological reviews · 2022Review
- Erratum: Type 1 regulatory T cell-mediated tolerance in health and disease.Frontiers in immunology · 2022Article
- Type 1 regulatory T cell-mediated tolerance in health and disease.Frontiers in immunology · 2022Review
- Review
- Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies.BMC genomics · 2019Article
- Lifestyle Factors Affecting the Gut Microbiota's Relationship with Type 1 Diabetes.Current diabetes reports · 2018Review
- Harnessing the power of regulatory T-cells to control autoimmune diabetes: overview and perspective.Immunology · 2018Review
- Molecular Mechanisms of T Cells Activation by Dendritic Cells in Autoimmune Diseases.Frontiers in pharmacology · 2018Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Dimeric Fc receptor (FcR) nonbinding anti-CD3 antibodies have been developed to minimize toxicities associated with classical anti-CD3 monoclonal antibodies (e.g., OKT3). Studies with murine analogs of non-FcR-binding antibodies have shown reduced mitogenicity compared to OKT3. In a trial of an FcR nonbinding humanized anti-CD3 mAb hOKT3gamma1(Ala-Ala) for treatment of patients with type 1 diabetes, we found significant increases in IL-10 and IL-5 in the serum of 63% and 72% of patients, respectively, and TNF-alpha and IL-6 levels that were lower than those previously reported following OKT3 therapy. The activation signal delivered by hOKT3gamma1(Ala-Ala) was associated with calcium signaling and cytokine production by previously activated human cells in vitro. However, the production of IL-10, compared to IFN-gamma on a molar basis, was greater after culture with hOKT3gamma1(Ala-Ala) than with OKT3. Flow cytometric studies confirmed that OKT3 induced IFN-gamma and IL-10 production, but hOKT3gamma1(Ala-Ala) induced only detectable IL-10 production in CD45RO(+) cells. Moreover, in vivo, we found IL-10(+)CD4(+) T cells after drug treatment. These cells were heterogeneous but generally CD45RO(+), CTLA-4(-), and expressed CCR4. A subgroup of these cells expressed TGF-beta. Thus, the non-FcR binding anti-CD3 mAb, hOKT3gamma1(Ala-Ala) delivers an activation signal to T cells that is quantitatively and qualitatively different from OKT3. It leads to the generation of T cells that might inhibit the autoimmune response and may be involved in the beneficial effect on beta cell destruction in Type 1 diabetes.
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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.