Dendritic cells for the induction of EBV immunity

Cell-mediated immunity provides resistance to Epstein-Barr virus (EBV), as demonstrated by the occurrence of EBV-induced post-transplant lymphoproliferative disease (PTLPD) in immunosuppressed patients. T cell immunity is stimulated most effectively by dendritic cells (DCs). Although DCs are not direct targets for infection by EBV, we tested whether EBV antigens are cross-presented by human DCs and whether DCs are efficient at stimulation of EBV-specific CD8+ T cells. We show that DCs cross-presenting apoptotic or necrotic lymphoblastoid cell lines (LCLs) are able to expand CD8+ T cells that directly recognize HLA-matched LCLs by IFN-gamma secretion and cytolytic activity. Part of this EBV-specific CD8+ T cell response was specific for the EBV nuclear antigen EBNA3 A and the latent membrane protein LMP2a. Both these antigens are expressed in PTLPD. In other EBV-associated malignancies such as Hodgkin' s lymphoma, T cell lymphoma and nasopharyngeal carcinoma, LMP2a is maintained. Therefore, the cross-presenting ability of DCs might be explored in DC-mediated active immunization against EBV-associated malignancies.