title: 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.
  
  
  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.
authors: Department of Gastrointestinal Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xian, Shan'Xi Province, China.
authors: J-F
authors: JF
authors: Du
authors: C
authors: C
authors: Wang
authors: W-Z
authors: WZ
authors: Wang
authors: M-B
authors: MB
authors: Li
authors: H-L
authors: HL
authors: Liang
authors: W-X
authors: WX
authors: Guan
mesh_terms: 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