EBV is a ubiquitous herpesvirus that causes transformation of lymphocytes and leads to a variety of neoplasms. Immunosuppressed individuals often have active EBV disease that results in the establishment of lymphomas. I propose that immunosuppressive drugs lead to downregulation of T cell function and immune dysregulation resulting in increased EBV growth and transformation of B cells. My primary objective will be to establish and characterize lymphoblastoid cell lines spontaneously derived from patients with detectable EBV infection. These cell lines are an authentic model of EBV infection because the EBV-transformation occurred in vivo. I will use these cell lines to evaluate the role of immunosuppressants in contributing to the development of EBV related lymphoproliferative disorders. I will measure Fas/Fas ligand expression and the potential for induction of apoptosis. In addition, I will characterize the role of bcl-2 proteins regulating cell death in these EBV transformed lines. These experimental cell lines can provide direct benefit for the patients from which they were derived and will be crucial in preparing potential prophylactic mechanisms for preventing EBV related disease in immunosuppressed patient populations.
