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Potential of tolerogenic dendritic cells for transplantation
A E Morelli1, H Hackstein, A W Thomson
1Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA. morelli@imap.pitt.edu
Abstract:
Dendritic cells (DC) are professional antigen (Ag)-presenting cells considered traditionally as the passenger leukocytes that, after migration from transplanted tissues, stimulate allospecific naive T cell responses and trigger acute rejection. However, there is recent evidence that, besides their role in central T lymphocyte deletion in the thymus, DC perform a crucial function to induce/maintain peripheral T cell tolerance. This paper outlines conceptual models that try to explain how DC may induce/maintain tolerance. It also considers how such ideas have been implemented recently in an effort to generate tolerogenic DC to induce donor Ag-specific tolerance/ immunosuppression and prolonged allograft survival. These approaches include genetic engineering of donor- or recipient-derived DC to express molecules capable of promoting tolerance to alloAg.