Cardiac and renal allograft rejection, vascular inflammation
Determine the effects of intermittent interactions of antibodies and complement
on endothelial cells.
Determine the mechanisms by which T cells promote antibody and complement
interactions with endothelial cells resulting in activatation and release
Determine the mechanisms by which complement interactions with endothelial
cells stimulate memory B cells resulting in local antibody production.
Modulation of T cell and B cell interactions with vascular endothelial
cells by antibodies, complement, and platelets
Advances in immunosuppression have decreased the incidence of acute rejection, but the survival of all organ transplants continues to be limited by chronic rejection. Until recently, experimental models of transplantation have focused primarily on the T cell arm of adaptive immunity as the entire cause of acute and chronic rejection. Based on our knowledge of T cells, increasingly sophisticated immunosuppressive regimens have been designed. Unfortunately, the current immunosuppressive protocols are not effective in preventing antibody-mediated rejection. Antibody responses to transplants continue to present practical clinical problems because many patients have been exposed to histocompatibility antigens by previous blood transfusions, transplants or pregnancy. Previous exposure to alloantigens is one of the major differences between clinical patients and most experimental models of transplantation. Although rejection can result from pure antibody-mediated rejection, more frequently rejection is part of a comprehensive immune response that includes some degree of cellular rejection. Cellular and humoral immunity are highly interactive responses. The mechanisms underlying these interactions are incompletely understood. The goal of our studies is to understand the mechanisms through which antibodies alter lymphocyte responses at the level of endothelial cells, platelets and leukocytes. These mechanisms have general relevance to vascular pathology.