Studies in allogeneic transplantation focus especially on mechanisms of antigen presentation, immune regulation, and tolerance. The primary immune barrier to the transplantation of organs and tissues between individuals of different species is the humoral immune response of the host against the graft. In all of these investigations, basic observations are validated by investigations in non-human primates and humans. One important subject of investigation is the manner in which endothelial cell functions are perturbed in immunity. Endothelium exists at the interface between the graft and the immune system of the graft recipient and there is compelling evidence that changes in the functions of endothelium give rise to the tissue manifestations of graft rejection.
Some projects focus especially on endothelium.
The projects include biochemical characterization of the antigens targeted by the immune system in xenotransplants and the application of genetic engineering to the modification of antigen expression. The response of endothelium to immune attack is studied by investigation aimed at the metabolism of heparan sulfate proteoglycan, a carbohydrate-protein conjugate that contributes to many of the important functions of blood vessels. Characterization of the enzymes which metabolize this substance in transplants and in tumors and development of agents that alter this metabolism are further goals. The targets of cellular immunity are the major histocompatibility antigens of the donor. How these antigens are presented to the graft recipient, particularly by the antigen presenting cells of the donor, is one other research focus.