Dendritic Cells Expand Epstein Barr Virus Specific CD8+ T Cell Responses More Efficiently Than EBV Transformed B Cells
- 作者：Marion Subklewe ; Kathrin Sebelin ; Andrea Block ; Antje Meier ; Anna Roukens ; Casper Paludan ; Jean-Franç ; ois Fonteneau ; Ralph M. Steinman and Christian Mü ; nz
- 关键词：Epstein Barr virus ; CD8+ T cells ; dendritic cells ; lymphoblastoid cell lines
- 刊名：Human Immunology
- 出版年：2005
- 期刊代码：75_01988859
- 类别：bio
- 出版时间：September 2005
- 卷：66
- 期：9
- 页码：938-949
- 文件大小：847 K
摘要
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.