Induction of tolerance to small bowel allografts in high-responder rats by combining anti-CD4 with CTLA4Ig.
This study was designed to investigate the effectiveness of combined perioperative anti-CD4 and human (h)CTLA4Ig therapy in preventing allorejection of small bowel transplantation in high-responder Lewis rat recipients of ACI grafts. Anti-CD4 (5 mg/kg x 4 days) or hCTLA4Ig (0.5 mg/rat x 2 days) therapy alone delayed, but did not prevent, allograft rejection after small bowel transplantation of ACI into Lewis rats. All grafts were rejected in 18 and 10 days, respectively. However, a regimen of anti-CD4 (5 mg/kg x 4 days) combined with hCTLA4Ig (0.5 mg/rat x 2 days) allowed indefinite survival of ACI small bowel allografts. Second donor-matched heart grafts were permanently accepted, whereas third-party (Sprague-Dawley) heart allografts were rejected by the tolerant recipients. These data suggest that these two reagents produced a synergistic effect in preventing allorejection of small bowel transplantation.
Yin
D P
DP
Department of Surgery, Stanford University School of Medicine, California 94305, USA.
Sankary
H N
HN
Williams
J
J
Krieger
N
N
Fathman
C G
CG
D000069594:Abatacept; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014184:Transplantation, Homologous / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000069594:Abatacept