Targeted deletion of Traf2 allows immunosuppression-free islet allograft survival in mice
| Autor: | Elisabeth K. Malle, Katherine A. Watson, Stacey N. Walters, Nicole L. La Gruta, Nathan W. Zammit, M. Saito, Robert Brink, Stephen I. Alexander, Shane T. Grey, Jeanette E. Villanueva |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male 0301 basic medicine TRAF2 Endocrinology Diabetes and Metabolism T cell medicine.medical_treatment Blotting Western Islets of Langerhans Transplantation CD8-Positive T-Lymphocytes Mice 03 medical and health sciences Internal Medicine medicine Animals Transplantation Homologous Cell Proliferation Immunosuppression Therapy Mice Knockout Mice Inbred BALB C geography CD40 geography.geographical_feature_category biology JNK Mitogen-Activated Protein Kinases Immunosuppression Flow Cytometry TNF Receptor-Associated Factor 2 Islet Mice Inbred C57BL 030104 developmental biology TNF receptor associated factor medicine.anatomical_structure Immunology biology.protein Female Antibody Intracellular |
| Zdroj: | Diabetologia. 60:679-689 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-016-4198-7 |
| Popis: | Administration of anti-CD40 ligand (CD40L) antibodies has been reported to allow long-term islet allograft survival in non-human primates without the need for exogenous immunosuppression. However, the use of anti-CD40L antibodies was associated with thromboembolic complications. Targeting downstream intracellular components shared between CD40 and other TNF family co-stimulatory molecules could bypass these complications. TNF receptor associated factor 2 (TRAF2) integrates multiple TNF receptor family signalling pathways that are critical for T cell activation and may be a central node of alloimmune responses.T cell-specific Traf2-deficient mice (Traf2TKO) were generated to define the role of TRAF2 in CD4Traf2TKO mice exhibited permanent survival of full MHC-mismatched pancreatic islet allografts without exogenous immunosuppression. Traf2TKO CD4Targeting TRAF2 may be useful as a therapeutic approach for immunosuppression-free islet allograft survival that avoids the thromboembolic complications associated with the use of anti-CD40L antibodies. |
| Databáze: | OpenAIRE |
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