EBV- infected B cells are dependent upon secretion of autocrine growth factors for growth and survival. This requirement is believed to apply to B cells naturally infected with EBV in vivo. Thus, it is critically important to characterize these molecules. Because these autocrine growth factors are only incompletely known, our goal is to define all the molecules responsible for growth of EBV-infected cells in vitro. Previous studies in our laboratory have demonstrated that IL-6 and lactic acid are two of the several molecules that stimulate autocrine growth of EBV-immortalized cells. The present studies are directed at purifying a third molecule that is distinguished from other previously described growth factors and which is capable of sustaining the growth of EBV-infected cells in vitro. Because this molecule is not present in large quantities in the supernatants of EBV-immortalized cells, its purification from other components represents a major undertaking. Over the last year, we have made great progress toward the purification by identifying several powerful separation steps. Post-transplant lymphoproliferative disease (PTLD) represents a severe and, often lethal, complication of severe immunosuppression associated with bone marrow and solid organ transplantation. As many as 25% of patients develop PTLD in association with regimens that include anti-T cell monoclonal antibody , Cyclosporin A, and T cell depletion of the donor's marrow with various methods including cell-separation devices, magnetic beads, monoclonal antibodies and Complement. PTLD is due to the in vivo outgrowth of B cells naturally infected with EBV and is a consequence of the absence of sufficient numbers of immune T cells normally involved in growth regulation of these cells and of abundance of growth factors. Our studies are immediately relevant to the study of safety of immunosuppressive regimens associated with PTLD because they are directed at understanding the mechanisms responsible for the growth of EBV-infected cells. DHP has primary product responsibility for IL-6 and cell separation devices, products linked with the occurrence of PTLD.
