Dendritic cells expand Epstein Barr virus specific CD8+ T cell responses more efficiently than EBV transformed B cells

Marion Subklewe, Kathrin Sebelin, Andrea Block, Antje Meier, Anna Roukens, Casper Paludan, Jean François Fonteneau, Ralph M. Steinman, Christian Münz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 stimulaton of EBV specific T cells in active or passive immunotherapy of EBV associated malignancies.

Original languageEnglish
Pages (from-to)938-949
Number of pages12
JournalHuman Immunology
Volume66
Issue number9
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • CD8 T cells
  • Dendritic cells
  • Epstein Barr virus
  • Lymphoblastoid cell lines

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