Passenger Leukocytes and the Immunogenicity of Skin Allografts

Skin grafts from tolerant mice and from mouse radiation chimeras are capable of inducing in isogeneic recipients a state of transplantation immunity that is indistinguishable from that induced by skin grafts from allogeneic donors. The immunizing isografts themselves are not rejected; they are only the vehicles of immunization. The immunogenicity of the isografts is related to the degree of leukocyte chimerism of the donors and to the number of leukocytes in the dermis, and it apparently is mediated by the transfer of small numbers of allogeneic "passenger leukocytes" from the chimeras to the normal hosts. Experiments with skin allografts indicate that passenger leukocytes are important immunogens under certain limiting conditions, e.g., when allografts are excised after only brief contact with their hosts. However, the contribution of passenger leukocytes to the aggregate immunogenicity of skin allografts under normal conditions probably is insignificant. Skin allografts from mice made profoundly leukopenic by pretreatment with whole-body irradiation or cyclophosphamide, or from chimeras whose leukocytes have been replaced by those of prospective graft recipients, do not survive any longer than controls. Nevertheless, the persistent immunogenicity of skin isografts from allogeneic hemopoietic chimeras and of skin allografts from intact mice after exposure of both types of donor to 1,200-R whole-body irradiation suggests that radioresistant, hemopoietically derived cells, probably Langerhans cells, might be important immunogens in skin allografts.