Combined Anti-CD154/CTLA4Ig Costimulation Blockade-Based Therapy Induces Donor-Specific Tolerance to Vascularized Osteomyocutaneous Allografts.
Am J Transplant
; 16(7): 2030-41, 2016 07.
Article
en En
| MEDLINE
| ID: mdl-26914847
ABSTRACT
Tolerance induction by means of costimulation blockade has been successfully applied in solid organ transplantation; however, its efficacy in vascularized composite allotransplantation, containing a vascularized bone marrow component and thus a constant source of donor-derived stem cells, remains poorly explored. In this study, osteomyocutaneous allografts (alloOMCs) from Balb/c (H2(d) ) mice were transplanted into C57BL/6 (H2(b) ) recipients. Immunosuppression consisted of 1 mg anti-CD154 on day 0, 0.5 mg CTLA4Ig on day 2 and rapamycin (RPM; 3 mg/kg per day from days 0-7, then every other day for 3 weeks). Long-term allograft survival, donor-specific tolerance and donor-recipient cell trafficking were evaluated. Treatment with costimulation blockade plus RPM resulted in long-term graft survival (>120 days) of alloOMC in 12 of 15 recipients compared with untreated controls (median survival time [MST] ≈10.2 ± 0.8 days), RPM alone (MST ≈33 ± 5.5 days) and costimulation blockade alone (MST ≈45.8 ± 7.1 days). Donor-specific hyporesponsiveness in recipients with viable grafts was demonstrated in vitro. Evidence of donor-specific tolerance was further assessed in vivo by secondary donor-specific skin graft survival and third-party graft rejection. A significant increase of Foxp3(+) regulatory T cells was evident in tolerant animals. Donor cells populated peripheral blood, thymus, and both donor and recipient bone marrow. Consequently, combined anti-CD154/CTLA4Ig costimulation blockade-based therapy induces donor-specific tolerance in a stringent murine alloOMC transplant model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades de la Piel
/
Donantes de Tejidos
/
Trasplante de Médula Ósea
/
Ligando de CD40
/
Colgajo Miocutáneo
/
Abatacept
/
Tolerancia Inmunológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2016
Tipo del documento:
Article
País de afiliación:
Taiwán