Transplantation tolerance induced by CTLA4-Ig.
The rejection of the transplanted allograft is dependent on T cell activation, which requires T cell receptor engagement by antigen and costimulatory signals delivered by T cell surface molecules such as CD28. CTLA4-Ig is a fusion protein that has previously been shown to block the CD28-mediated costimulatory signal and inhibit immune responses in vitro and in vivo. In this report we show that treatment of the C3H/He recipient of a BALB/c vascularized cardiac allograft with a 12-day course of CTLA4-Ig produced indefinite graft survival (> 100 days) in the majority of recipients. In addition, these recipients demonstrated donor-specific transplantation tolerance when tested with donor-specific (BALB/c) and third-party (C57BL/10) skin grafts. These results demonstrate that CTLA4-Ig can induce transplantation tolerance in the adult murine cardiac allograft model.
Pearson
T C
TC
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322.
Alexander
D Z
DZ
Winn
K J
KJ
Linsley
P S
PS
Lowry
R P
RP
Larsen
C P
CP
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D060908:CTLA-4 Antigen; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates; D007143:Immunoglobulin Heavy Chains / Q000494:pharmacology; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007143:Immunoglobulin Heavy Chains; D011993:Recombinant Fusion Proteins; D000069594:Abatacept