Beneficial Effects of Simultaneous Treatment With 15-deoxyspergualin and Monoclonal Antibodies to CD45RB and CD154 on Murine Islet Transplantation Recipients
| Autor: | Sung-Joo Kim, Hea-Jung Park, E.‐S. Lee, Jienny Lee, Da-Yeon Jung, Hae-Jung Lee, Chi-Young Chang, Eun Young Kim, Ghee-Young Kwon, Jae-Won Joh, Suk-Koo Lee |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Gusperimus medicine.drug_class T-Lymphocytes medicine.medical_treatment Xenotransplantation CD40 Ligand Transplantation Heterologous Islets of Langerhans Transplantation Pharmacology Biology Monoclonal antibody Guanidines Diabetes Mellitus Experimental Mice Internal medicine Immune Tolerance medicine Animals Transplantation Homologous Mice Inbred BALB C Transplantation geography Glucose tolerance test geography.geographical_feature_category medicine.diagnostic_test Antibodies Monoclonal Immunotherapy Flow Cytometry Islet Rats Blockade Endocrinology Cytokines Leukocyte Common Antigens Immunosuppressive Agents medicine.drug |
| Zdroj: | Transplantation. 82:188-195 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/01.tp.0000226175.94546.18 |
| Popis: | Background. Treatment of transplant recipients with either 15-deoxyspergualin (DSG) or monoclonal antibodies (mAbs) to T-cell proteins CD45RB and CD154 (a two-signal blockade) has been shown to prolong islet graft survival. Therefore, we investigated the combined effect of DSG, anti-CD45RB, and anti-CD 154 in murine islet model. Methods. Chemically induced diabetic C57BL/6 mice underwent allografting with islets from BALB/c mice or xenografting with rat islets. After transplantation, they were treated with either DSG, the two-signal blockade, or both (the triple treatment). The tolerogenic effects of the posttransplant treatments were measured with an intraperitoneal glucose tolerance test (IPGTT), immunohistology, enzyme-linked immunosorbent assays, and flow cytometry. Results. Blood glucose profiles measured after glucose challenges were improved in all islet recipients. Enhancement of xenograft survival in triple-treated groups was not statistically significant (P=0.08), compared to graft survival in group received only the two-signal blockade. However, 15 days after transplantation, xenografts in the triple-treated group showed a significant decrease in the proportion of CD4 + , CD8 + , and CD4 + CD45RB high T-cells, and in the expression of interleukin-10 and interferon-γ, relative to grafts in the other treatment groups. In addition, reduced infiltration of the xenografts by CD3 + T-cells was observed in groups that had received either the two-signal blockade or the triple treatment. With long-term (>248 days) xenografts, only those in the triple-treated group were free of inflammatory infiltrates. These grafts also exhibited larger islet clusters and contained more insulin- and glucagon-positive cells, relative to grafts in the other treatment groups. Conclusion. Triple treatment has a beneficial effect in murine islet xenotransplantation. |
| Databáze: | OpenAIRE |
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