A NOVEL-APPROACH TO EXTEND THE SURVIVAL OF SKIN XENOGRAFTS WITHOUT ENTAILING GENERAL IMMUNOSUPPRESSION OR SYSTEMIC TOXICITY

The feasibility of using antigenically disguised skin xenotransplants to cover extensive burns for a suitable time lag without administering immunosuppressive drugs was tested experimentally. Pieces of human sk in that had been preincubated for 3 h at 37-degrees-C with either mous e anti-human beta2-microglobulin monoclonal antibody (beta2m-McAb) or PBS (controls) were grafted onto the backs of immunologically competen t Swiss mice, and the time required for their rejection or substitutio n by normal autogenous skin was determined. Thus, it was found that th e beta2m-McAb-pretreated xenografts had a significantly longer mean su rvival time than the control grafts. An even longer skin xenograft MST was obtained when beta2m-MrAb was repeatedly injected, at weekly inte rvals, just beneath the transplants. Parallel immunohistochemical stud ies showed that the beta2m-McAb entered the grafts and was bound to it s targets both in epidermis and dermis, Moreover, a small amount of be ta2m-McAb administered at the outset significantly hindered the reacti ve proliferation of primed mouse spleen cells cultured in the presence of human epidermal cells. Finally, neither toxic effects nor a weaken ing of immune competence were elicited by repeated intraperitoneal inj ections of beta2m-McAb. Therefore, it seems expedient to propose the u se of beta2m-McAb to delay the rejection of skin xenografts as this an tibody harmlessly prevents, wholly or in part, the activation of the r ecipients' lymphocytes. This would positively aid any patient urgently needing xenograft cover of extensive burns.