6533b7cefe1ef96bd12578f6

RESEARCH PRODUCT

RELEVANCE OF MESENCHYMAL THYMUS CELLS (MC) FOR ACCEPTANCE OF ALLOGENEIC MATURE THYMUS GRAFTS AND INDUCTION OF ALLOTOLERANCE IN NUDE MICE

subject

description

Allogeneic thymus (aTh) from an adult immunocompetent donor cannot be transplanted successfully in thymusless nude mice even if the graft is irradiated. The graft is destroyed for unknown reasons and no immunocompetence is achieved in the host. Two approaches were established to achieve acceptance of aTh. In experiment 1, mature aTh was transplanted in nude mice, after specific tolerance to the recipient was induced in the donor during the neonatal period. This resulted in acceptance of the aTh, immunological reconstitution and tolerance to the donor's and recipient's MHC-haplotype as proved by skin-grafts and MLC. In experiment 2, neonatal thymus was grafted into allogeneic nude mice and retransplanted 6 weeks later into nude mice syngeneic to the thymus donor.Before retransplantation, investigation of the thymus tissue by monoclonal antibodies showed predominant MHC-antigen expression of the allogeneic host's haplotype on the intrathymic MCs. Again,acceptance and immunological reconstitution was obtained; tolerance to the MHC-haplotype present on the intrathymic allogeneic MCs was observed. These results demonstrate that mature aTh can be successfully transplanted if "intrathymic" tolerance to the recipient has been induced during the immature status of the thymus. After acceptance of the thymus, tolerance to the donor and recipient MHC-haplotype is achieved, apparently transmitted by the intrathymic MCs. "Intrathymic tolerance induction", therefore, may provide a new approach in the treatment of thymus-deficient patients.