Induction of transplantation tolerance by intraportal injection of allogeneic bone marrow cells. Possible implications for intrauterine bone marrow transplantation across major histocompatibility barriers.
Intraportal inoculation of C57BL/6 marrow cells into sublethally (400 rad) irradiated BALB/c recipients resulted in durable chimerism and the permanent acceptance of C57BL/6 skin allografts. Sublethally irradiated recipients of a similar number of marrow cells inoculated systemically did not develop chimerism or any significant prolongation of the survival of C57BL/6 skin allografts. Consequently, lethal graft-versus-host disease developed only in recipients of intraportal marrow allografts (80%). The intraportal injection of allogeneic C57BL/6 marrow cells into nonirradiated recipients resulted in significant, although not permanent, prolongation of skin allograft survival without durable chimerism, suggesting that the introduction of alloantigens intraportally may favor the induction of nonresponsiveness to alloantigens even across strong major histocompatibility barriers. The relevance of these findings is discussed regarding the intraportal inoculation of allogeneic bone marrow cells for the treatment of genetic disorders in utero through the induction of neonatal tolerance.
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Department of Surgery, Hadassah University Hospital, Jerusalem, Israel.
Morecki
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Slavin
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D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D002678:Chimera; D006085:Graft Survival / Q000528:radiation effects; D006086:Graft vs Host Disease / Q000276:immunology; D007108:Immune Tolerance; D007267:Injections; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012882:Skin Tests; D016038:Skin Transplantation; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation