Dendritic Cells Expand Epstein Barr Virus Specific CD8 super(+) T Cell Responses More Efficiently Than EBV Transformed B Cells

• Published in: Human Immunology Vol. 66; no. 9; pp. 938 - 949
• Main Authors: Subklewe, Marion, Sebelin, Kathrin, Block, Andrea, Meier, Antje, Roukens, Anna, Paludan, Casper, Fonteneau, Jean-Francois, Steinman, Ralph M, Muenz, Christian
• Format: Journal Article
• Language: English
• Published: 01.01.2005
• Subjects: Epstein-Barr virus
• ISSN: 0198-8859; 1365-2567
• DOI: 10.1016/j.humimm.2005.07.003

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 super(+) T cell stimulation against dominant and subdominant EBV antigens. DCs expanded tenfold more EBNA3A and LMP2 specific CD8 super(+) 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 stimulaton of EBV specific T cells in active or passive immunotherapy of EBV associated malignancies.