Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154
| Autor: | Michele Masetti, Maria Chatzipetrou, Allan D. Kirk, Linda Burkly, David M. Harlan, Camillo Ricordi, Alessandra Ranuncoli, Maria Oliveira, Norma S. Kenyon, Joseph L. Wagner |
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| Rok vydání: | 1999 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Transplantation Heterotopic medicine.medical_treatment Lymphocyte CD40 Ligand Islets of Langerhans Transplantation Biology Antibodies chemistry.chemical_compound Pancreatectomy Internal medicine Insulin Secretion medicine Animals Humans Insulin Transplantation Homologous Immunosuppression Therapy geography Membrane Glycoproteins Multidisciplinary geography.geographical_feature_category C-Peptide C-peptide Graft Survival Immunosuppression Biological Sciences Islet Mixed lymphocyte reaction Macaca mulatta Transplantation Diabetes Mellitus Type 1 surgical procedures operative Endocrinology medicine.anatomical_structure Liver chemistry Toxicity |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:8132-8137 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.96.14.8132 |
| Popis: | Reported effects of anti-CD154 treatment on autoimmunity, alloreactivity, and inflammatory events mediated by macrophages and endothelial cells indicated that it might be an ideal agent for the prevention of intrahepatic islet allograft failure. This hypothesis was tested in MHC-mismatched rhesus monkeys. Transplantation of an adequate number of viable islets resulted in engraftment and insulin independence in six of six recipients treated with anti-CD154 (hu5c8) induction plus monthly maintenance therapy (post-operative day >125, >246, >266, >405, >419, >476). Anti-CD154 (hu5c8) displayed no inhibitory effect on islet cell function. For monkeys followed for >100 days, continued improvement in graft function, as determined by first phase insulin release in response to intravenous glucose, was observed after the first 100 days post-transplant. No evidence of toxicity or infectious complications has been observed. All recipients treated with anti-CD154 became specifically nonresponsive to donor cells in mixed lymphocyte reactions. Furthermore, three monkeys are now off therapy (>113, >67, and >54 days off anti-CD154), with continued insulin independence and donor-specific mixed lymphocyte reaction hyporeactivity. In striking contrast to all previously tested strategies, transplantation of an adequate number of functional islets under the cover of anti-CD154 (hu5c8) monotherapy consistently allows for allogeneic islet engraftment and long-term insulin independence in this highly relevant preclinical model. |
| Databáze: | OpenAIRE |
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