- Prof. Angus Thomson, Principal Investigator
- Dr. Adrian Morelli, Co-Investigator
- Dr. Petra O’Conell, Associate
- Dr. Mohamed H. Sayegh, Consultant
- Dr. Charles Maliszewski, Consultant
- University of Pittsburgh, Pittsburgh, USA
- Studies of a novel cellular regulator of host response to organ transplants
The host response to organ transplants is initiated and controlled by specialised 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 led either to graft rejection or acceptance. Although DC have been studied by a small number of research groups for the past 25 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 characterisation. This new knowledge includes recognition that DC are much more diverse in character and function than previously recognised. Amongst these recent discoveries is the identification of a major novel population of DC termed lymphoid DC (LDC). Based on limited studies to date it has been suggested that while DC that have been studied for may years ("myeloid" DC or "MDC") are primarily instigators of immune responses, the newly identified LDC 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 characterise LDC in terms of their functional interactions with T lymphocytes from unrelated ("foreign") individuals, both using cell culture techniques and following the injection of LDC into experimental animals (mice) including recipients of organ (hearts) grafts. It is expected that these LDC will demonstrate the potential to modulate host responses to organ transplants and that the results will provide a basis for further evaluation of their therapeutic potential.