Poor long term patient survival(60% at 2 years) in lung allograft recipients are mainly due to rejection and complications associated with the use of nonspecfic immunosuppressants. Better means to achieve graft acceptance is desperately needed. I
have
investigated whether mixed allogeneic chimerism in the form of bon emarrow stem cell engraftment would induce donor-specific tolerance for lung allografts. Fisher(F344)and Wistar Furth(WF)rats were lethally irradiated(1100cGy)and reconstituted
with
a
mixture of T-cell depleted syngeneic and allogeneic bone marrow(F344+WF→WF, ACI+F344→F344). After Mixed chimerism was documented by peripheral blood lymphocyte typing at 28 days, orthotopic left single lung transplantation was performed, using
donor-specific or third party allografts. No immunosuppressants were administered. Graft rejection was monitored by chest rentgenography, and confirmed by histology.
Mixed chimeric rats accepted lung allografts permanently, kand it was not strain specific effect. Tolerance Was all or none phenomenon which had nothing to do with the percentage of chimerism. Mixed chimeras rejected third party allcgrafts in
less
than
10 days, a time course similar to that of unmanipulated controls. No acute or chronic rejection was observed in donor specific grafts more than 150 days posttransplant. These data suggest that mixed chimerism in the form of bone marrow stem cell
engraftment results in stable, systemic donor-specific transplantation tolerance for lung allografts.
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