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

A new strategy for organ allografts that does not require recourse to immun osuppressants is established in mice. The strategy includes sublethal (7 Gy ) irradiation followed by the injection of donor bone marrow cells (BMCs) v ia the portal vein (P.V.) and organ allografts 1 day after irradiation. Irr adiation doses (less than or equal to7 Gy) are found to allow the recipient s to survive without the need to reconstitute the BMCs, as the recipient he matolymphoid cells can gradually recover, One hundred percent of recipients irradiated with 7 Gy followed by either P.V, or i.v. injection of donor BM Cs accept organ allografts (the skin, pancreas, and adrenal glands) for mor e than 1 year. However, organ allograft survival rates decrease when irradi ation 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 BM Cs induces persistent tolerance more effectively than the i.v. injection. H -2 typing reveals that almost all the hematolymphoid cells (>98%) in the pe ripheral blood and hematolymphoid organs are donor-derived even 1 year afte r the treatment (7 Gy and P.V.). The T cells are tolerant to both donor-typ e and host-type MHC determinants. The major mechanism underlying the persis tent tolerance induced by this strategy seems to be because of clonal delet ion. This simple and safe strategy mould be of great advantage for human or gan transplantation.