- Prof. Angus W. Thomson, Principal Investigator
- Dr. An De Creus, Co-Investigator
- Dr. Zhiliang Wang, Research Associate
- Bs. Jason F. Duncan, Research Technician
- University of Pittsburgh, Pittsburgh, USA
- Plasmacytoid Dendritic Cells and Liver Transplant Tolerance
The host response to organ transplants is initiated and controlled by specialized white blood cells termed dendritic cells (DC) that are present in the graft and in the blood and lymph glands of the host. Elucidation of the role(s) of these cells in presenting foreign (antigenic) material and in regulating the immune response is crucial to further understanding the mechanisms that lead either to graft rejection or acceptance.
Although DC have been studied for the past 30 years, there has been a recent dramatic increase in our understanding of the properties of these cells based on technologic advances that permit their enhanced production and characterization. This new knowledge includes recognition that DC are much more diverse in character and function than previously recognized. Amongst these recent discoveries is the identification of a major novel population of DC termed ‘plasmacytoid’ DC that can be induced to produce a molecule (IDO) that inhibits immunity. Based on limited studies to date, it has been suggested that while DC that have been studied for many years are primarily instigators of immune responses, the newly identified plasmacytoid DC may be more important in immune regulation, including the potential to promote “tolerance” (permanent donor-specific unresponsiveness) to “foreign“ material (antigens) as represented by an organ transplant.
This research project will more fully characterize plasmacytoid DC from liver DC in terms of their functional interactions with T lymphocytes from unrelated (“foreign”) individuals, both using cell culture techniques and following the injection of DC into experimental animals (mice) including recipients of liver transplants. It is expected that these DC will demonstrate potential to modulate host responses to organ transplants and that the results will provide a basis for further evaluation of their therapeutic potential.