Activated B Cells Mediate Efficient Expansion of Rare Antigen-Specific T Cells

Caroline Zentz; Martina Wiesner; Stephen Man; Bernhard Frankenberger; Barbara Wollenberg; Peter Hillemanns; Reinhard Zeidler; Wolfgang Hammerschmidt; Andreas Moosmann

doi:10.1016/j.humimm.2006.12.004

Activated B Cells Mediate Efficient Expansion of Rare Antigen-Specific T Cells

Caroline Zentz, Martina Wiesner, Stephen Man, Bernhard Frankenberger, Barbara Wollenberg, Peter Hillemanns, Reinhard Zeidler, Wolfgang Hammerschmidt, Andreas Moosmann^*

^*Corresponding author for this work

Department of Otorhinolaryngology, Phoniatrics and Pediatric Audiology

14 Citations (Scopus)

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.

Original language	English
Journal	Human Immunology
Volume	68
Issue number	2
Pages (from-to)	75-85
Number of pages	11
ISSN	0198-8859
DOIs	https://doi.org/10.1016/j.humimm.2006.12.004
Publication status	Published - 02.2007

Funding

We thank Chris Boswell and Julian Hickling (Cambridge, UK) for kindly providing vaccinia viruses (SR16 and Wyeth), and Gabriele Hollweck, Adam Slusarski and Sabine Eichenlaub (Munich, Germany) for assistance with TCR clonotyping. This study was supported by the Deutsche Forschungsgemeinschaft (SFB455) and H.W. & J. Hector-Stiftung.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.humimm.2006.12.004

Cite this

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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 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.",

author = "Caroline Zentz and Martina Wiesner and Stephen Man and Bernhard Frankenberger and Barbara Wollenberg and Peter Hillemanns and Reinhard Zeidler and Wolfgang Hammerschmidt and Andreas Moosmann",

note = "Funding Information: We thank Chris Boswell and Julian Hickling (Cambridge, UK) for kindly providing vaccinia viruses (SR16 and Wyeth), and Gabriele Hollweck, Adam Slusarski and Sabine Eichenlaub (Munich, Germany) for assistance with TCR clonotyping. This study was supported by the Deutsche Forschungsgemeinschaft (SFB455) and H.W. \& J. Hector-Stiftung.",

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AU - Zentz, Caroline

AU - Wiesner, Martina

AU - Man, Stephen

AU - Frankenberger, Bernhard

AU - Wollenberg, Barbara

AU - Hillemanns, Peter

AU - Zeidler, Reinhard

AU - Hammerschmidt, Wolfgang

AU - Moosmann, Andreas

N1 - Funding Information: We thank Chris Boswell and Julian Hickling (Cambridge, UK) for kindly providing vaccinia viruses (SR16 and Wyeth), and Gabriele Hollweck, Adam Slusarski and Sabine Eichenlaub (Munich, Germany) for assistance with TCR clonotyping. This study was supported by the Deutsche Forschungsgemeinschaft (SFB455) and H.W. & J. Hector-Stiftung.

PY - 2007/2

Y1 - 2007/2

N2 - 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.

AB - 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.

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Activated B Cells Mediate Efficient Expansion of Rare Antigen-Specific T Cells

Abstract

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UN SDGs

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