Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin.
Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000917:Antibody Formation; D000954:Antigens, Surface / Q000276:immunology; D016026:Bone Marrow Transplantation; D003630:Daunorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control; D006410:Hematopoiesis; D007121:Immunocompetence; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011828:Radiation Chimera; D013154:Spleen / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018800:Thy-1 Antigens; D003630:Daunorubicin