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 anti...

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Bibliographic Details
Published in:Human immunology 2007-02, Vol.68 (2), p.75-85
Main Authors: Zentz, Caroline, Wiesner, Martina, Man, Stephen, Frankenberger, Bernhard, Wollenberg, Barbara, Hillemanns, Peter, Zeidler, Reinhard, Hammerschmidt, Wolfgang, Moosmann, Andreas
Format: Article
Language:English
Subjects:
Activated B cells
Allergy and Immunology
antigen-presenting cells
Antigen-Presenting Cells - immunology
B-Lymphocytes - immunology
CD40 Antigens - immunology
CD8 T cells
CD8-Positive T-Lymphocytes - immunology
Cells, Cultured
Epitopes, T-Lymphocyte - immunology
HLA-A2 Antigen - immunology
HLA/peptide tetramers
Human papillomavirus 16
Humans
immunotherapy
Immunotherapy - methods
Lymphocyte Activation
Oncogene Proteins, Viral - chemical synthesis
Oncogene Proteins, Viral - immunology
Papillomavirus E7 Proteins
Species Specificity
T-Lymphocyte Subsets - immunology
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Summary: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 106 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.
ISSN:0198-8859
1879-1166
DOI:10.1016/j.humimm.2006.12.004