A STRATEGY FOR ORGAN ALLOGRAFTS WITHOUT USING IMMUNOSUPPRESSANTS OR IRRADIATION

A strategy to achieve regular and long lasting organ and tissue allogr afts without using immunosuppressants and/or irradiation has been esta blished for mice. One hundred percent of skin allografts can be induce d to survive >350 days after transplantation if spleen cells from the same donors are first injected into the portal vein of the recipients. The mechanisms underlying this long-term tolerance induction can be d escribed as follows: (i) donor T cells from the spleen of the donor fa cilitate the acceptance of the allogeneic engraftment, (ii) donor-spec ific energy is induced in the cytotoxic T-lymphocytes of the recipient s, (iii) T helper type 2 cells became the dominant T cells in the reci pients that are accepting the skin transplants, and tip) a lasting chi merism (microchimerism) is established in these recipients. This strat egy, perhaps with minor modifications, might permit one also to overco me major barriers to organ allografting in humans. If this were the ca se, it could represent production of long lasting immunologic toleranc e without need for irradiation or cytotoxic chemo-preparative regimen and as such could greatly facilitate allotransplantation free of episo des of chronic or acute rejection or toxic and damaging preparatory re gimens.