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Transferable cardiac allograft acceptance induced by transfusion of donor B cells with impaired inducible costimulator/B7h allorecognition.

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 AND METHODS: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.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Du JF,Wang C,Wang WZ,Li MB,Liang HL,Guan WX

doi

10.1016/j.transproceed.2009.01.106

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

1840-3

issue

5

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(09)00283-8

journal_volume

41

pub_type

杂志文章

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