Prolonged limb allograft survival with CD 40 costimulation blockade, T-cell depletion, and megadose donor bone-marrow transfusion.
The purpose of this study was to determine the efficacy of a treatment regimen consisting of CD 40 costimulation blockade, T-cell depletion, and megadose donor bone marrow transfusion in the limb allograft model. C57Bl/6 mice underwent limb transplantation from Balb/c mice and received MR1 (anti-CD 40 ligand monoclonal antibody), and CD4(+) and CD8(+) T cell-depleting antibodies with and without 120 x 10(6) donor bone-marrow transfusion. Recipients treated only with antibodies showed rejection at 51.4+/-17 (mean+/-SEM) days, while those who also received donor bone marrow had allograft survival of 67+/-16.4 days, with a range up to 91 days. Treated specimens with rejection had less lymphocytic infiltration than untreated controls. Recipients of donor bone marrow also demonstrated early mixed chimerism, which disappeared after 1 month. While allograft survival was prolonged, tolerance was not achieved, and the mechanism of rejection was more consistent with a chronic process.
Tung
Thomas H
TH
Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA. tungt@msnotes.wustl.edu
Mackinnon
Susan E
SE
Mohanakumar
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D016026:Bone Marrow Transplantation; D016025:Bone Transplantation / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D046528:Chimerism; D006085:Graft Survival / Q000276:immunology*; D006614:Hindlimb / Q000637:transplantation*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016133:Polymerase Chain Reaction; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens