Prolonged islet graft survival in NOD mice by blockade of the CD40-CD154 pathway of T-cell costimulation. 2001

R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
Diabetes Research Institute, University of Miami School of Medicine, Florida 33136, USA.

Allorejection and recurrence of autoimmunity are the major barriers to transplantation of islets of Langerhans for the cure of type 1 diabetes in humans. CD40-CD154 (CD40 ligand) interaction blockade by the use of anti-CD154 monoclonal antibody (mAb) has shown efficacy in preventing allorejection in several models of organ and cell transplantation. Here we report the beneficial effect of the chronic administration of a hamster anti-murine CD154 mAb, MR1, in prolonging islet graft survival in NOD mice. We explored the transplantation of C57BL/6 islets into spontaneously diabetic NOD mice, a combination in which both allogeneic and autoimmune components are implicated in graft loss. Recipients were treated either with an irrelevant control antibody or with MR1. MR1 administration was effective in prolonging allograft survival, but did not provide permanent protection from diabetes recurrence. The autoimmune component of graft loss was studied in spontaneously diabetic NOD mice that received syngeneic islets from young male NOD mice. In this combination, a less dramatic yet substantial delay in diabetes recurrence was observed in the MR1-treated recipients when compared with the control group. Finally, the allogeneic component was explored by transplanting C57BL/6 islets into chemically induced diabetic male NOD mice. In this setting, long-term graft survival (>100 days) was achieved in MR1-treated mice, whereas control recipients rejected their grafts within 25 days. In conclusion, chronic blockade of CD154 results in permanent protection from allorejection and significantly delays recurrence of diabetes in NOD mice.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D003920 Diabetes Mellitus A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte

Related Publications

R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
January 2009, Diabetes,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
September 2019, Xenotransplantation,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
December 2008, Transplantation,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
August 2004, Diabetes,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
May 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
January 1998, Cell transplantation,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
April 2001, Investigative ophthalmology & visual science,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
October 2009, Journal of pineal research,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
November 2021, Xenotransplantation,
R D Molano, and T Berney, and H Li, and P Cattan, and A Pileggi, and C Vizzardelli, and N S Kenyon, and C Ricordi, and L C Burkly, and L Inverardi
January 2001, Transplantation proceedings,
Copied contents to your clipboard!