Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation.
Ag-specific T cell activation requires a CD28-mediated costimulatory interaction. This observation has suggested novel approaches to suppress donor-specific immunity, including the use of soluble CD28 antagonists, such as CTLA4Ig, which suppresses transplant rejection in small animal models. In this study, CTLA4Ig therapy was examined in a non-human primate model of allogeneic pancreatic islet transplantation. Two of five CTLA4Ig-treated monkeys showed prolonged graft survival, which correlated with donor-specific hyporesponsiveness in vitro. Humoral responses to the transplanted tissue were suppressed in all treated animals. These results suggest that CTLA4Ig is effective in suppressing both humoral and cellular immune responses in a non-human primate model of allogeneic transplantation.
Levisetti
M G
MG
Department of Surgery, University of Chicago, IL 60637, USA.
Padrid
P A
PA
Szot
G L
GL
Mittal
N
N
Meehan
S M
SM
Wardrip
C L
CL
Gray
G S
GS
Bruce
D S
DS
Thistlethwaite
J R
JR
Bluestone
J A
JA
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D060908:CTLA-4 Antigen; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D006085:Graft Survival; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007518:Isoantibodies / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D008252:Macaca fascicularis; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014184:Transplantation, Homologous
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007518:Isoantibodies; D011993:Recombinant Fusion Proteins; D000069594:Abatacept