Dendritic cells expand Epstein Barr virus specific CD8+ T cell responses more efficiently than EBV transformed B cells.
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.
Subklewe
Marion
M
Department of Hematology/Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. marion.subklewe@charite.de
Sebelin
Kathrin
K
Block
Andrea
A
Meier
Antje
A
Roukens
Anna
A
Paludan
Casper
C
Fonteneau
Jean-François
JF
Steinman
Ralph M
RM
Münz
Christian
C
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
D000954:Antigens, Surface; D000956:Antigens, Viral