title: Dendritic cells expand Epstein Barr virus specific CD8+ T cell responses more efficiently than EBV transformed B cells.
abstract: Adoptive transfer of Epstein Barr virus (EBV) specific cytotoxic T lymphocytes (CTLs) has been successfully applied in the treatment of EBV associated post-transplant lymphoproliferative disease (PTLD). In most studies EBV transformed B cells (LCLs) have been used for the induction of EBV specific T cell lines. Application of this approach to other EBV associated tumors is difficult, because LCLs focus T cell expansion toward immunodominant EBV antigens that are not expressed in EBV associated Hodgkin's lymphoma and nasopharyngeal carcinoma. Therefore, we compared dendritic cells (DCs) with LCLs for CD8+ T cell stimulation against dominant and subdominant EBV antigens. DCs expanded tenfold more EBNA3A and LMP2 specific CD8+ T cells than LCL and also stimulated EBV specific CTL from PTLD patients. Both, DCs and LCLs stimulations led to the expansion of high affinity T cells, capable to target EBV transformed B cells. While LCLs and DCs expressed MHC class I and II products at similar levels, DCs showed a higher expression of costimulatory and adhesion molecules. This resulted in more efficient T cell conjugate formation with DCs than with LCLs. We propose the use of DCs for stimulation of EBV specific T cells in active or passive immunotherapy of EBV associated malignancies.
authors.affiliation: Department of Hematology/Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. marion.subklewe@charite.de
authors.forename: Marion
authors.initials: M
authors.lastname: Subklewe
authors.forename: Kathrin
authors.initials: K
authors.lastname: Sebelin
authors.forename: Andrea
authors.initials: A
authors.lastname: Block
authors.forename: Antje
authors.initials: A
authors.lastname: Meier
authors.forename: Anna
authors.initials: A
authors.lastname: Roukens
authors.forename: Casper
authors.initials: C
authors.lastname: Paludan
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fonteneau
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D000954:Antigens, Surface; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D003713:Dendritic Cells / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology; D008213:Lymphocyte Activation; D017735:Virus Latency
chemical_list: D000954:Antigens, Surface; D000956:Antigens, Viral