Orthotopic bone transplantation in mice. III. Methods of reducing the immune response and their effect on healing.
Various methods of reducing the immune response to allogeneic bone grafts, either by pretreating the graft or by immunosuppressing the recipient, were compared. Tibial grafts from B10.D2 mice, either untreated or pretreated in various ways, were transplanted into B10 recipients. The antibody response was followed and the extent of bone healing at 4 months was assessed. Pretreatment of the graft by X-irradiation, freezing, or by incubation in alloantisera (either anti-H-2 or anti-Ia) reduced or abolished the immunogenicity of the graft. Immunosuppression of the recipient with methotrexate or antilymphocyte serum (ALS) also greatly depressed the antibody response. But when healing was assessed, none of these treatments except ALS improved the delayed healing of the bone allografts. The reason for this failure was probably that X-irradiation, freezing, alloantiserum pretreatment, and methotrexate all interfered with bone healing directly, whereas ALS did not. We conclude that many methods will reduce the immune response to allogeneic bone, but that only ALS will improve the healing of the allogeneic bone. Furthermore, as a corollary to the observation that pretreatment with anti-Ia serum markedly reduced the immunogenicity of bone allografts, we conclude that much of the immunogenicity of bone allografts is attributable to a population of Ia-positive cells.
D000818:Animals; D000917:Antibody Formation; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000528:radiation effects; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D013977:Tibia / Q000637:transplantation*; D013997:Time Factors; D014184:Transplantation, Homologous; D014945:Wound Healing / Q000187:drug effects / Q000528:radiation effects; D014965:X-Rays
D000961:Antilymphocyte Serum; D008727:Methotrexate