| Titolo | Microencapsulated G3C hybridoma cell graft delays the onset of spontaneous diabetes in NOD mice by an expansion of GITR1 Treg cells |
|---|---|
| Tipo di pubblicazione | Articolo su Rivista peer-reviewed |
| Anno di Pubblicazione | 2020 |
| Autori | Cari, Luigi, Montanucci Pia, Basta Giuseppe, Petrillo Maria Grazia, Ricci Erika, Pescara Teresa, Greco Alessia, Cipriani Sabrina, Shimizu Jun, Migliorati Graziella, Nocentini Giuseppe, Calafiore Riccardo, and Riccardi Carlo |
| Rivista | Diabetes |
| Volume | 69 |
| Paginazione | 965 – 980 |
| Type of Article | Article |
| ISSN | 00121797 |
| Parole chiave | alginic acid, animal, animal cell, animal experiment, animal model, Animals, Antibodies, article, B lymphocyte, CD3+ T lymphocyte, CD4+ T lymphocyte, Cell Encapsulation, Cell expansion, cell proliferation, controlled study, diabetes mellitus, enzyme linked immunosorbent assay, Enzyme-Linked Immunosorbent Assay, Female, Flow cytometry, g3c monoclonal antibody, gene expression regulation, genetics, glucocorticoid induced tumor necrosis factor receptor, Glucocorticoid-Induced TNFR-Related Protein, Glucose, glucose blood level, humoral immunity, hybridoma, Hybridomas, Inbred NOD, insulin dependent diabetes mellitus, interleukin 2 receptor alpha, Knockout, knockout mouse, messenger RNA, metabolism, Mice, microcapsule, Monoclonal, Monoclonal antibody, mouse, nonhuman, nonobese diabetic mouse, pancreas, pancreas islet, pancreatic lymph node, physiology, priority journal, protein expression, real time polymerase chain reaction, Regulatory, regulatory T lymphocyte, Spleen, spleen cell, systemic lupus erythematosus, T-Lymphocytes, Tnfrsf18 protein, transcription factor FOXP3, Type 1, unclassified drug, wild type |
| Abstract | As an alternative to lifelong insulin supplementation, potentiation of immune tolerance in patients with type 1 diabetes could prevent the autoimmune destruction of pancreatic islet b-cells. This study was aimed to assess whether the G3c monoclonal antibody (mAb), which triggers the glucocorticoid-induced TNFR-related (Gitr) costimulatory receptor, promotes the expansion of regulatory T cells (Tregs) in SV129 (wild-type) and diabetic-prone NOD mice. The delivery of the G3c mAb via G3C hybridoma cells enveloped in alginate-based microcapsules (G3C/cps) for 3 weeks induced Foxp31 Treg-cell expansion in the spleen of wild-type mice but not in Gitr2/2 mice. G3C/cps also induced the expansion of nonconventional Cd41Cd252/lowFoxp3lowGitrint/high (GITR single-positive [sp]) Tregs. Both Cd41Cd251GitrhighFoxp31 and GITRsp Tregs (including also antigen-specific cells) were expanded in the spleen and pancreas of G3C/cps-treated NOD mice, and the number of intact islets was higher in G3C/cps-treated than in empty cps-treated and untreated animals. Consequently, all but two G3C/cpstreated mice did not develop diabetes and all but one survived until the end of the 24-week study. In conclusion, long-term Gitr triggering induces Treg expansion, thereby delaying/preventing diabetes development in NOD mice. This therapeutic approach may have promising clinical potential for the treatment of inflammatory and autoimmune diseases. © 2020 by the American Diabetes Association. |
| Note | Cited by: 6; All Open Access, Bronze Open Access |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083767637&doi=10.2337%2fdb19-0087&partnerID=40&md5=45b17330c7b662e448c7f117ce59150c |
| DOI | 10.2337/db19-0087 |
| Citation Key | Cari2020965 |
| PubMed ID | 32169893 |
