Combined treatment with CD40 costimulation blockade, T-cell depletion, low-dose irradiation, and donor bone marrow transfusion in limb allograft survival.
To determine the efficacy of a regimen based on CD40 costimulation blockade and donor bone marrow in the limb allograft model, C57Bl/6 mice received limb allografts from Balb/c mice and either no treatment or a combination of MR1 (anti-CD40 ligand monoclonal antibody), CD4+ and CD8+ T-cell-depleting antibodies, low-dose irradiation, and bone marrow transfusion from Balb/c donors for 1 or 2 weeks. Recipients treated for 1 week showed rejection at 38.2 +/- 5.4 (mean +/- SEM) days, while those treated for 2 weeks had allograft survival of 56.5 +/- 9.9, with a range up to 91 days. Histology demonstrated rejection which was less cell-mediated and suggestive of transplant vasculopathy. Differential rejection of skin occurred first. Thus, a combined regimen based on CD40 costimulatory blockade and donor marrow significantly prolonged allograft survival. However, tolerance was not achieved, and histology suggests chronic rejection as a possible cause of allograft loss.
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; D000917:Antibody Formation; D016026:Bone Marrow Transplantation / Q000379:methods*; D019013:CD40 Antigens / Q000276:immunology / Q000627:therapeutic use*; D004307:Dose-Response Relationship, Radiation; D005121:Extremities / Q000528:radiation effects* / Q000601:surgery*; D006085:Graft Survival; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011897:Random Allocation; D014184:Transplantation, Homologous
D019013:CD40 Antigens