Enhancement of thyroid allograft survival following organ culture .2. Induction of recipient peripheral tolerance

Hyperbaric oxygen culture (HOC) prolongs endocrine graft survival and decreases major histocompatibility complex (MHC) class I surface expression. If graft prolongation were the result of passenger cell inactivation and decreased class I expression, then simultaneous transplantation of both a nontreated and a HOC-created graft should result in rejection of the nontreated graft and acceptance of the HOC-treated graft. Simultaneous transplant of a nontreated and a HOC-treated thyroid allograft beneath the kidney capsule of recipient mice resulted in prolonged survival of both grafts in three strain combinations differing at class I(K-K, D-d, D-b). In vitro analysis of the recipient splenic population revealed the presence of primed donor-specific cytotoxic T cells. These results suggest that recipient tolerance was not because of anergy or clonal deletion. Splenectomy at the time of transplant, revealed that both graft prolongation and the induction of recipient tolerance were dependent on the spleen. Finally, analysis of graft infiltrating cells reveals the presence of CD8(+) cells but no CD4(+) cells in tolerant recipients, whereas graft infiltrating cells from rejecting recipients contained both populations. The results suggest that active peripheral tolerance can be generated following transplantation of a HOC-treated allograft and that tolerance results from redirection of the recipients immune response. (C) American Society for Histocompatibility and Immunogenetics, 1997.