ArticleEuropean journal of immunology2012
T cells interact with T cells via CD40-CD154 to promote autoimmunity in type 1 diabetes.
Article in European journal of immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Identification of potential new T cell activation molecules: a Bioinformatic Approach.Scientific reports · 2024Article
- Small-molecule inhibitors of the CD40-CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models.Frontiers in immunology · 2024Article
- SOCS3 inhibits the mesenchymal stromal cell secretory factor SDF-1-mediated improvement of islet function in non-obese diabetic mice.Stem cell research & therapy · 2023Article
- Targeting Type 1 Diabetes: Selective Approaches for New Therapies.Biochemistry · 2019Review
- Design, Synthesis, and Evaluation of Novel Immunomodulatory Small Molecules Targeting the CD40⁻CD154 Costimulatory Protein-Protein Interaction.Molecules (Basel, Switzerland) · 2018Article
- Dichotomous roles of co-stimulatory molecules in diabetes mellitus.Oncotarget · 2018Review
- Small-Molecule Inhibitors of the CD40-CD40L Costimulatory Protein-Protein Interaction.Journal of medicinal chemistry · 2017Article
- The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel Diseases (IBDs).PloS one · 2015Article
- TL1A increases expression of CD25, LFA-1, CD134 and CD154, and induces IL-22 and GM-CSF production from effector CD4 T-cells.PloS one · 2014Article
- Cutting edge: CD4 T cells reactive to an islet amyloid polypeptide peptide accumulate in the pancreas and contribute to disease pathogenesis in nonobese diabetic mice.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Agonistic anti-CD40 promotes early development and increases the incidence of severe thyroid epithelial cell hyperplasia (TEC H/P) in CD4-/- mice.Immunity, inflammation and disease · 2013Article
- Immunological cell type characterization and Th1-Th17 cytokine production in a mouse model of Gaucher disease.Molecular genetics and metabolism · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
We have investigated the role of CD40 signaling in islet-reactive, diabetogenic CD4(+) Th1 T-cell clones. Using multispectral flow cytometry, we showed that CD40 and CD154 are co-expressed and form complexes on the surface of activated T cells. We also demonstrate that activated Tcells can transactivate CD4(+) CD40(+) T cells through the CD40-CD154 pathway. To investigate the role of CD40 signaling on Th1 cells, we used the diabetogenic clone BDC-5.2.9 retrovirally transduced with a truncated form of the CD40 molecule to produce a CD40 dominant-negative T-cell clone. Upon challenge with antigen in vitro, the production of IFN-γ by BDC-5.2.9 CD40DN was greatly reduced and, in vivo, the dominant-negative variant was unable to induce diabetes. Transduction with the CD40DN vector was also effective in preventing transfer of disease by primary NOD CD4(+) T cells. Ex vivo analysis of pancreatic infiltrates after transfer of BDC-5.2.9 CD40DN cells revealed an overall reduction of cell numbers and cytokine production by both T cells and macrophages. These data indicate that CD40 is an important signaling molecule on autoreactive CD4(+) T cells and contributes to their pathogenic effector function.
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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.