Donor marrow-derived cells as immunogens and targets for the immune response to bone and skin allografts

The relative importance of donor marrow-derived cells in the immunogenicity of bone and skin allografts was compared. Radiation chimeras were created to have marrow-derived cells (MDCs) of a different genotype from their nonmarrow-derived cells (NMDCs). Such animals were used as donors of bone or skin for recipients chosen so that either the MDCs or the NMDCs of the graft would be incompatible. Immunogenicity was determined by measuring the recipient antibody response. The effect of the immune response on the bone graft (rejection) was determined by impaired bone healing. When MDCs alone were H-2 disparate with the recipient, bone grafts were immunogenic, and the bone graft healing was impaired. In contrast, skin grafts in the same combinations were immunogenic but were not rejected if the differences were only expressed on the MDCs of the graft. The role of NMDCs in all of these experiments was more difficult to interpret, but the results suggested that NMDCs are relatively unimportant for healing of bone grafts, although critical for rejection of skin grafts. We conclude that, unlike the situation with skin grafts, the major inducers and targets of the immune response to bone allografts are marrow derived.