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Type I diabetes mellitus is an immune-mediated disease and characterized by loss of insulin producing beta cells in pancreas
leading to insulin deficiency. Autoreactive T cells play a key role in beta-cell destruction during the disease progression.
Selective elimination of autoreactive T cells and replacement of destructed islet cells are the ultimate goal for treatment of type
1 diabetes. Allogeneic islet transplantation may be considered as a therapeutic approach for the treatment of type 1 diabetes.
However clinical application of this approach is limited by allograft rejection. The rejection is initiated by alloreactive T cells
beside long-term use of immunosuppressive medications which are associated with a broad range of side effects. Therefore, novel
approaches that control rejection in the absence of chronic immunosuppression will have significant impact on the field of islet
transplantation. Activated T cells up-regulates Fas and FasL on their cell surface and upon re-activation with same antigen they
become sensitive to FasL-mediated apoptosis. Therefore, selective elimination of alloreactive T cells will not only eliminate the
need to use of immunosuppressive drugs but also protects allogeneic islet graft from rejection with intact immune response to
unrelated antigens or pathogens. Towards this end, we have constructed and produced a novel form of FasL protein which is
chimeric with streptavidin (SA-FasL). We have engineered pancreatic islets using biotin as a bridge to display SA-FasL chimeric
protein on the surface of allogeneic islets in a rapid and efficient manner without any unfavorable effect on the function of islets.
Transplantation of SA-FasL-engineered islets into diabetic allogeneic recipients resulted in tolerance and treatment of diabetes.
Therefore, the direct display of immunological ligands on the surface of islets serves as a rapid, efficient, and clinically applicable
approach for immunomodulation with implications in clinical islet transplantation.
Esma S. Yolcu is an Assistant Professor of Microbiology and Immunology, Director of Imaging Facility at the Institute for Cellular Therapeutics, and
member of James Brown Cancer Center, University of Louisville, Louisville, KY. After receiving her Ph.D. from University of Ankara, Turkey, she
joined the Institute for Cellular Therapeutics at the University of Louisville to pursue her postdoctoral training followed by promotion to a faculty
position in the Department of Microbiology and Immunology. Her research focuses on the modulation of the immune system for the treatment of
autoimmunity and graft rejection. Her work has been funded by various federal and nonfederal funding agencies, including NIH, American Heart
Association, and American Diabetes Association. She is the recipient of several awards, member of various national and international societies,
serves on Editorial Board of scientific journals, and published over 67 peer-reviewed papers, abstracts, and review articles in high ranking journals,
such as Immunity, Circulation, and Journal of Immunology.
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