Operational tolerance is early acquired and long maintained in 50% liver allograft transplantation

Abstract

Lifelong anti-rejection therapy is mandatory to weaken the host immune system and maintain the graft functions after organ transplantation, its toxicities and side-effects incidentally elicit mortalities and morbidities. Operational tolerance is a long immunosuppression-free state in which the allograft functions well and no immunological rejections occur, and no operational tolerance is clinically in use. Here we introduce that operational tolerance, based on hypertrophy to hyperplasia switch upon liver regeneration, is early achieved and maintained well in half-size liver allograft transplantation through host bone marrow stem cells repopulation and 9-day immunosuppression. Compared with whole and partial rat liver transplantations as the controls, longer-term survivals (over 430 days) were observed in the tolerant hosts (p= 0.001), the allografts functioned well and no acute or chronic rejections were confirmed by histology examinations. Further study revealed that the allograft was reinstituted by host-derived stem cells marked with CD34, which migrated, repopulated and differentiated after mobilization. However donor-specific hyporesponse was not achieved through skin transplantation, indicating no adaptive immune activity occurrence. Our protocol is characteristic of targeting the allografts and almost no immunological intervention, offering a novel avenue to operational tolerance induction which is of highly clinical relevance.