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


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.
Du
J-F
JF
Department of Gastrointestinal Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xian, Shan'Xi Province, China.
Wang
C
C
Wang
W-Z
WZ
Li
M-B
MB
Liang
H-L
HL
Guan
W-X
WX
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous / Q000276:immunology