Costimulation and autoimmune diabetes in BB rats
| Autor: | Aldo A. Rossini, Danny Zipris, Jean Leif, HA Drexhage, Dale L. Greiner, Mohammed Javeed I. Ansari, Jan Rozing, T Hunig, Christopher D. Benjamin, Hideo Yagita, Britte C. Beaudette-Zlatanova, Barbara J. Whalen, Henk Groen, Mohamed H. Sayegh, John P. Mordes |
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| Přispěvatelé: | Internal Medicine, Erasmus MC other, Immunology |
| Rok vydání: | 2006 |
| Předmět: |
MONOCLONAL-ANTIBODY
Islets of Langerhans Transplantation chemical and pharmacologic phenomena medicine.disease_cause Immune tolerance Autoimmunity CD28 Antigens SDG 3 - Good Health and Well-being Recurrence RECENT THYMIC EMIGRANTS VERSUS-HOST-DISEASE Immune Tolerance Animals Immunology and Allergy Medicine Rats Inbred BB Pharmacology (medical) TRANSPLANTATION TOLERANCE IN-VIVO NOD mice Autoimmune disease Type 1 diabetes tolerance diabetes business.industry autoimmunity rodent Antibodies Monoclonal hemic and immune systems medicine.disease NOD MICE Rats Blockade Transplantation Disease Models Animal Diabetes Mellitus Type 1 T-CELL COSTIMULATION HUMORAL IMMUNE-RESPONSE Immunology OX40 LIGAND business CARDIAC ALLOGRAFT-REJECTION Biobreeding rat transplantation |
| Zdroj: | American Journal of Transplantation, 6(5), 894-902. Wiley-Blackwell Publishing Ltd American Journal of Transplantation, 6(5), 894-902. Wiley |
| ISSN: | 1600-6135 |
| Popis: | Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55-120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process. |
| Databáze: | OpenAIRE |
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