ArticleThe Journal of clinical investigation2010
Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed.
- The therapeutic potential of mesenchymal stem cells-derived extracellular vesicles/exosomes on the diabetes: a systematic review study.Diabetology & metabolic syndrome · 2025Review
- TNF Production or TNFR2 Expression Characterize Distinct States of Regulatory T Cells that Cooperate in Treg Expansion in Cancer and Chronic Inflammation.European journal of immunology · 2025Article
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Tregs from human blood differentiate into nonlymphoid tissue-resident effector cells upon TNFR2 costimulation.JCI insight · 2024Article
- Teplizumab in Type 1 Diabetes Mellitus: An Updated Review.TouchREVIEWS in endocrinology · 2023Review
- Pancreatic draining lymph nodes (PLNs) serve as a pathogenic hub contributing to the development of type 1 diabetes.Cell & bioscience · 2023Review
- Functional interrogation of lymphocyte subsets in alopecia areata using single-cell RNA sequencing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- 2D and 3D cultured human umbilical cord-derived mesenchymal stem cell-conditioned medium has a dual effect in type 1 diabetes model in rats: immunomodulation and beta-cell regeneration.Inflammation and regeneration · 2022Article
- Advancing Biologic Therapy for Refractory Autoimmune Hepatitis.Digestive diseases and sciences · 2022Review
- TNFR2 antagonist and agonist: a potential therapeutics in cancer immunotherapy.Medical oncology (Northwood, London, England) · 2022Review
- Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges.Stem cell research & therapy · 2022Review
- TNFR2 blockade of regulatory T cells unleashes an antitumor immune response after hematopoietic stem-cell transplantation.Journal for immunotherapy of cancer · 2022Article
- TNFR2 Costimulation Differentially Impacts Regulatory and Conventional CD4Frontiers in immunology · 2022Review
- Role of Cytokines in Thymic Regulatory T Cell Generation: Overview and Updates.Frontiers in immunology · 2022Review
- The dichotomous outcomes of TNFα signaling in CD4Frontiers in immunology · 2022Review
- The Mechanisms of Effector Th Cell Responses Contribute to Treg Cell Function: New Insights into Pathogenesis and Therapy of Asthma.Frontiers in immunology · 2022Review
- Immunoregulated insulitis and slow-progressing type 1 diabetes after duodenopancreatectomy.Diabetologia · 2021Article
- Article
- Ion therapy of pulmonary fibrosis by inhalation of ionic solution derived from silicate bioceramics.Bioactive materials · 2021Article
- Regulatory T cells enhance Th17 migration in psoriatic arthritis which is reversed by anti-TNF.iScience · 2021Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4+CD25+Foxp3+ Tregs play a major role in prevention of autoimmune diseases. The suppressive effect of Tregs on effector T cells (Teffs), the cells that can mediate autoimmunity, has been extensively studied. However, the in vivo impact of Teff activation on Tregs during autoimmunity has not been explored. In this study, we have shown that CD4+ Teff activation strongly boosts the expansion and suppressive activity of Tregs. This helper function of CD4+ T cells, which we believe to be novel, was observed in the pancreas and draining lymph nodes in mouse recipients of islet-specific Teffs and Tregs. Its physiological impact was assessed in autoimmune diabetes. When islet-specific Teffs were transferred alone, they induced diabetes. Paradoxically, when the same Teffs were cotransferred with islet-specific Tregs, they induced disease protection by boosting Treg expansion and suppressive function. RNA microarray analyses suggested that TNF family members were involved in the Teff-mediated Treg boost. In vivo experiments showed that this Treg boost was partially dependent on TNF but not on IL-2. This feedback regulatory loop between Teffs and Tregs may be critical to preventing or limiting the development of autoimmune diseases.
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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.