Transferable cardiac allograft acceptance induced by transfusion of donor B cells with impaired inducible costimulator/B7h allorecognition.
Transplant Proc
; 41(5): 1840-3, 2009 Jun.
Article
em En
| MEDLINE
| ID: mdl-19545740
ABSTRACT
OBJECTIVE:
Donor-specific transfusion (DST) of leukocytes with an impaired costimulatory signal has been proven to be an effective way to improve allograft survival. Inducible costimulator (ICOS) has been shown to play a crucial role in acute and chronic allograft rejection. To test the role of ICOS signaling during DST, we employed ICOS-Fc-targeted B cells as antigen of DST to challenge the allogeneic engraftment in vivo. MATERIALS ANDMETHODS:
A murine cardiac allograft model was employed using BALB/c donors and C57BL/6 recipients, while various transfusions were performed according to treatment protocols.RESULTS:
Allograft survival was prolonged by infusion of ICOS-Fc-targeted B cells; however, allograft acceptance could not be achieved unless additional systemic injections of ICOS-Fc were given. Adoptive transfer of splenic CD4(+) but not CD4(+)CD25(-) subsets from long-term allograft survival (LTAS) mice to lightly irradiated naive recipients resulted in subsequent BALB/c allograft acceptance without additional immunosuppression.CONCLUSIONS:
ICOS/B7h signaling during direct allorecognition played an important role in prolonging allograft survival, and an allograft acceptance can be established by DST with complete blockade of ICOS/B7h in both direct and indirect allorecognition. Interestingly, this allograft acceptance was transferable and maintained at least partly by the immune regulation of CD4(+)CD25(+) T cells. These findings may help to design a potential therapeutic treatment to prevent allograft rejection by DST in combination with ICOS/B7h blockade.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Transplante de Coração
/
Transfusão de Linfócitos
/
Sobrevivência de Enxerto
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article