INDUCTION OF UNRESPONSIVENESS TO SKIN AND HEART ALLOGRAFTS IN MICE BY A SYNERGISTIC TREATMENT WITH PROCARBAZINE, ANTILYMPHOCYTE SERUM, AND DONOR-TYPE CELLS

Abstract

SUMMARY The survival of BALB/c skin allografts on CBA mice subjected to an immunosuppressive “pulse” consisting of a short combined treatment with procarbazine and antilymphocyte serum (ALS) after grafting was studied. Graft survival was modified by additionally injected donor strain thymocytes or bone marrow cells. An i.v. cell injection 6-16 days before grafting and immunosuppressive treatment was most effective. Two zones of cell dosage, particularly very small doses, caused accelerated graft rejection. A potentiation of the action of ALS was provided by procarbazine. A low, well tolerated supplement of this drug increased more than 10-fold the effect of a moderate dose of ALS. Inferior ALS-sparing effects or none at all were encountered with cyclophosphamide, cytosine arabinoside. and colchicine. Procarbazine alone, as well as the combined regimen, also effectively prolonged the survival of BALB/c heart allografts in C3H hosts. The cardiac grafts were also protected by the passive administration of antiserum. Xenograft. Survival was prolonged only slightly by the immunosuppressive pulse and impaired by prior cell injection. Spleen cells from mice carrying long standing BALB/c allografts displayed reactivity against BALB/c antigens in a graft-versus-host assay