title: Activated B cells mediate efficient expansion of rare antigen-specific T cells.
abstract: Potent professional antigen-presenting cells (APC) are essential tools to activate and expand antigen-specific T cells in vitro for use in adoptive immunotherapy. CD40-activated B cells can be easily generated and propagated from human donors and have been successfully used to generate antigen-specific T-cell cultures. Here we show that CD40-activated B cells strongly and specifically expand rare populations of antigen-specific CD8 T cells, with frequencies of less than 1 in 20,000 CD8 T cells in peripheral blood. We focused on T cells recognizing an epitope from the human papillomavirus 16 (HPV-16) E7 protein. In 6 of 6 healthy donors, epitope-specific CD8+ T cells were found to be "rare" by this criterion, as shown by staining with human leukocyte antigen (HLA)/peptide multimers. Using peptide-loaded CD40-activated B cells, epitope-specific T cells could be selectively expanded in all donors up to 10(6) fold, and the resulting T-cell cultures contained up to 88% specific T cells. These results strongly encourage the use of CD40-stimulated B cells as APCs in immunotherapy.
authors.affiliation: Clinical Cooperative Group Molecular Oncology, GSF - National Research Center for Environment and Health, Munich, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Zentz
authors.forename: Martina
authors.initials: M
authors.lastname: Wiesner
authors.forename: Stephen
authors.initials: S
authors.lastname: Man
authors.forename: Bernhard
authors.initials: B
authors.lastname: Frankenberger
authors.forename: Barbara
authors.initials: B
authors.lastname: Wollenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.forename: Reinhard
authors.initials: R
authors.lastname: Zeidler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hammerschmidt
authors.forename: Andreas
authors.initials: A
authors.lastname: Moosmann
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation; D009856:Oncogene Proteins, Viral / Q000138:chemical synthesis / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16