Combination therapy with anti-ICOS and cyclosporine enhances cardiac but not islet allograft survival.
The blockade of costimulatory signals is a powerful strategy to prevent allograft rejection and facilitate transplantation tolerance. In recent years, a series of novel costimulatory molecules have been identified, including an inducible costimulatory molecule (ICOS). To date, little has been uncovered regarding the therapeutic potential of blocking ICOS signaling in the setting of transplantation. In a fully MHC-mismatched mouse model, we studied the effect of blocking ICOS signaling using a specific monoclonal antibody (anti-ICOS mAb) in combination with cyclosporine on cardiac and islet allograft survival. We demonstrated that combined treatment with anti-ICOS mAb and cyclosporine can induce long-term graft acceptance in cardiac but not islet allografts, suggesting that the type of transplanted tissue significantly influences the immunologic patterns of graft acceptance or rejection in this model.
Nanji
S A
SA
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Hancock
W W
WW
Anderson
C C
CC
Zhu
L F
LF
Kneteman
N M
NM
Shapiro
A M J
AM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018106:CD28 Antigens / Q000276:immunology*; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D013997:Time Factors; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine