Dr. Ginny Bumgardner continues her investigations in transplant immunobiology, using experimental models of pancreatic islet and hepatocyte (liver cell) transplantation. Dr. Bumgardner’s lab-based research focuses on basic mechanisms of alloimmune mediated hepatocyte injury. She introduced the functional hepatocyte transplantation model using transgenic hepatocytes to study the in vivo immunobiology of allogeneic hepatocellular transplantation in 1998.
Published work demonstrates that allogeneic hepatocytes are vulnerable to cell-mediated as well as alloantibody-mediated parenchymal cell damage. Her studies using this model in comparison to genetically matched islet transplant and heart transplant, have demonstrated the importance of tissue (parenchymal cell type) in determining the phenotype and effector mechanisms comprising alloimmune responses after transplantation. Work from her lab has demonstrated that allogeneic liver parenchymal cells stimulate the maturation of CD4-independent and CD4-dependent allospecific CD8+ cytolytic effectors (allo-CTLs). This pathway is important because it can cause transplant tissue damage, either early or late after transplant, and interferes with the induction of transplantation tolerance. These CTL subsets are distinct in magnitude of in vivo cytotoxic effector function, CD8+ T cell recall responses in vivo and molecular effector mechanisms, which mediate cytotoxicity.
Furthermore, these two pathways are differentially susceptible to conventional and experimental immunosuppressive agents. Dr. Bumgardner’s laboratory was the first to report the efficacy of a novel immunosuppressive strategy that successfully suppresses this immunoresistant (CD4-independent) CD8+ T cell mediated immune pathway and promotes long-term allograft survival. Very little is known regarding how CD8+ T cells cause immune damage of allografts and in vivo effector functions of alloreactive CD8+ T cells is a specific focus for investigation.
Dr. Bumgardner’s lab is also investigating CD4-dependent humoral immune pathways of allograft damage. Her lab is the first to show that alloantibodies also mediate immune damage of transplanted hepatocytes by a macrophage-dependent, complement-independent, NK-independent cytotoxic effector mechanism. Studies are ongoing to investigate novel mechanisms governing the regulation of post transplant alloantibody production in an animal model and to investigate translational aspects of these studies in humans. These and other projects have been funded by external sponsors, such as the American Diabetes Association, the Roche Organ Transplant Research Foundation, the American Society of Transplant Surgeons, the American Society of Transplantation and the National Institutes of Health.