A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed by injection of donor bone marrow cells via portal vein.

Abstract

A new strategy for organ allografts that does not require recourse to immunosuppressants is established in mice. The strategy includes sublethal (7 Gy) irradiation followed by the injection of donor bone marrow cells (BMCs) via the portal vein (P.V.) and organ allografts 1 day after irradiation. Irradiation doses (< or =7 Gy) are found to allow the recipients to survive without the need to reconstitute the BMCs, as the recipient hematolymphoid cells can gradually recover. One hundred percent of recipients irradiated with 7 Gy followed by either P.V. or i.v. injection of donor BMCs accept organ allografts (the skin, pancreas, and adrenal glands) for more than 1 year. However, organ allograft survival rates decrease when irradiation doses are reduced; the skin graft survival rate of mice treated with 6.5 Gy and P.V. injection of BMCs is 79%, whereas that of mice treated with 6.5 Gy and i.v. injection is 50%, indicating that the P.V. injection of BMCs induces persistent tolerance more effectively than the i.v. injection. H-2 typing reveals that almost all the hematolymphoid cells (>98%) in the peripheral blood and hematolymphoid organs are donor-derived even 1 year after the treatment (7 Gy and P.V.). The T cells are tolerant to both donor-type and host-type MHC determinants. The major mechanism underlying the persistent tolerance induced by this strategy seems to be because of clonal deletion. This simple and safe strategy would be of great advantage for human organ transplantation.