Beneficial effects of simultaneous treatment with 15-deoxyspergualin and monoclonal antibodies to CD45RB and CD154 on murine islet transplantation recipients.
Transplantation
; 82(2): 188-95, 2006 Jul 27.
Article
en En
| MEDLINE
| ID: mdl-16858281
ABSTRACT
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-CD154 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 CD4CD45RB T-cells, and in the expression of interleukin-10 and interferon-gamma, 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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trasplante de Islotes Pancreáticos
/
Antígenos Comunes de Leucocito
/
Ligando de CD40
/
Diabetes Mellitus Experimental
/
Guanidinas
/
Inmunosupresores
/
Anticuerpos Monoclonales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Transplantation
Año:
2006
Tipo del documento:
Article