Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649614
Title: The role of the intra-hepatic immune response following liver transplantation in allograft rejection and acceptance
Author: Dollinger, M. M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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Abstract:
Compared to other solid organs following transplantation, the liver is unique as an allograft, more resistant to rejection and accepted without immunosuppression in many animal models. The aim of this thesis was to analyse the allogeneic immune response within the graft following liver transplantation and to examine the role of hepatic cells in graft rejection or acceptance. This might allow the better understanding of the specific features of the immune response towards liver grafts and open new therapeutic approaches to organ transplantation. Dendritic cells (DC) are important regulators of immune responses including allograft rejection and are in particular equipped in activating naïve T lymphocytes. Using a mouse model, hepatic DC were isolated by adapting a novel method via immuno-magnetic separation, and compared to isolated renal and splenic DC. Although hepatic DC were found to have a unique composition with a high percentage of lymphoid-derived DC, functional differences between DC subpopulations in stimulating allogeneic T lymphocytes were not evident. The DC function was rather dependent on the cytokine environment with induction of a Th1 response following activation with GM-CSF and abrogation of the Th1 response after pre-incubation with TGF-β or CTLA-41g, but not IL-10. In conclusion, these studies provide evidence for a modification of the allogeneic immune response within the liver allograft affecting the cell fate of the infiltrating cells as well as of the target cells. Although hepatic donor cells might contribute to this modification, their interaction with the infiltrating immune cells appears to be strongly dependent on the cytokine environment. This however would implicate, that the resistance of liver allografts to rejection and ultimately graft acceptance is open to manipulation and could be achieved in other organs, too.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.649614  DOI: Not available
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