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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 8/2005

01-08-2005 | Original Article

Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses

Authors: Thomas Felzmann, Katharina Gabriele Hüttner, Sabine Konstanze Breuer, Doris Wimmer, Gabriele Ressmann, Dagmar Wagner, Petra Paul, Manfred Lehner, Andreas Heitger, Wolfgang Holter

Published in: Cancer Immunology, Immunotherapy | Issue 8/2005

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Abstract

Dendritic cells (DC) are candidates for antigen-presenting cells that present exogenous antigen on MHC class I molecules to cytotoxic T lymphocytes (CTL), a process referred to as cross-priming. We triggered interleukin (IL)-12 release from DC, which was limited to the first day after maturation induction, by a combination of lipopolysaccharide (LPS) and interferon (IFN)-γ. To stimulate T lymphocytes, we used soluble protein derived from lysis of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) or ovalbumin loaded onto DC. Co-culture was initiated 2–6 or 48 h after maturation corresponding to “semi-mature” actively IL-12-secreting type 1 DC (sm-DC1) or a “fully mature” DC1 that had lost the ability to release IL-12 (fm-DC1), respectively. IL-12-secreting sm-DC1 but not fm-DC1 efficiently triggered cytolytic activity in autologous T lymphocytes. The combination of IL-1β, IL-6, TNF-α, and prostaglandin E2 generated type 2 DC that did not secrete IL-12 (DC2) and could not prime T-cell cytolytic activity. However, supplementation of cultures using DC2 with IL-12 resulted in CTL activity while the presence of anti-IL-12 monoclonal antibodies in cultures using IL-12 secreting sm-DC1 suppressed CTL activity. Thus, actively IL-12-secreting sm-DC1 are necessary and sufficient for the antigen-specific expansion of CTL in response to exogenously provided soluble antigen.
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Metadata
Title
Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses
Authors
Thomas Felzmann
Katharina Gabriele Hüttner
Sabine Konstanze Breuer
Doris Wimmer
Gabriele Ressmann
Dagmar Wagner
Petra Paul
Manfred Lehner
Andreas Heitger
Wolfgang Holter
Publication date
01-08-2005
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 8/2005
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-004-0637-2

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