Research Group

  • Dr. Ginny Bumgardner, Principal Investigator
  • Ms. Anna Marie Hummel, Research Associate
  • Mr. Thomas Pham, Research Associate


  • Ohio State University, Columbus, USA


  • Analysis of a Novel Strategy which Suppresses Aggressive (CD4-Independent) CD8+ T-Cell-Initiated Hepatocyte Rejection
Most current immunotherapeutic agents interfere with CD4+ T-cell-dependent rejection

Most current immunotherapeutic agents interfere with CD4+ T-cell-dependent rejection. Work from our laboratory and others has identified an aggressive CD8-dependent rejection response which is CD4 independent and not susceptible to a variety of immunotherapeutic strategies that readily control CD4-dependent rejection responses. We have used a unique functional model of hepatocyte transplantation to separately assess the effect of various interventions on CD8- and CD4-dependent rejection processes. Recently, we have demonstrated that a novel immunosuppressive strategy, which targets lymphocyte function associated antigen 1 (LFA-1) and CD40/CD40L costimulation, suppresses both aggressive CD8-dependent and CD4-dependent rejection responses. This proposal will investigate how this strategy influences T cell recruitment and activation. In addition, we will determine whether this short-term immunosuppressive strategy results in the development of regulatory T cells, which permit long-term hepatocellular allograft survival. These studies involve the transplantation of purified hepatocytes into host mice, which are treated with monoclonal antibodies directed at LFA-1 and CD40L. Host tissue will be analysed by immunohistochemical means to determine the influence of the treatment strategy upon recruitment of host inflammatory cells to lymph nodes, spleen and liver tissue. Host inflammatory cells at these sites will also be isolated and analysed by flow cytometry for expression of various phenotypic and activation markers to determine the influence of the therapy upon cell subset recruitment, activation and function. Mice with long-term hepatocellular allograft survival induced by treatment with anti-LFA-1 and anti-CD40L mAbs will be assessed for the presence of regulatory T cells. In addition, host cells will be tested for evidence of immunoregulation in in vitro assays.
The successful regulation of immune damage of allogeneic hepatocytes will advance the therapeutic modality in patients with liver disease who could be cured or supported by successful hepatocyte transplantation.