Transplantation tolerance and autoimmunity after xenogeneic thymus transplantation

Successful grafting of vascularized xenografts (Xgs) depends on the ability to reliably induce both T cell-independent and -dependent immune tolerance , After temporary NK cell depletion, B cell suppression, and pretransplant infusion of donor Ags, athymic rats simultaneously transplanted with hamste r heart and thymus Xgs developed immunocompetent rat-derived T cells that t olerated the hamster Xgs but provoked multiple-organ autoimmunity. The auto immune syndrome was probably due to an insufficient development of toleranc e for some rat organs; for example, it led to thyroiditis in the recipient rat thyroid, but not in simultaneously transplanted donor hamster thyroid, Moreover, grafting a mixed hamster/rat thymic epithelial cell graft could p revent the autoimmune syndrome. These experiments indicate that host-type t hymic epithelial cells may be essential for the establishment of complete s elf-tolerance and that mixed host/donor thymus grafts may induce T cell xen otolerance while maintaining self-tolerance in the recipient.