title: Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses.
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)-gamma. 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-1beta, IL-6, TNF-alpha, 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.
authors.affiliation: Children's Cancer Research Institute, St. Anna Children's Hospital, Kinderspitalgasse 6, 1090 Vienna, Austria. thomas.felzmann@ccri.univie.ac.at
authors.forename: Thomas
authors.initials: T
authors.lastname: Felzmann
authors.forename: Katharina Gabriele
authors.initials: KG
authors.lastname: Hüttner
authors.forename: Sabine Konstanze
authors.initials: SK
authors.lastname: Breuer
authors.forename: Doris
authors.initials: D
authors.lastname: Wimmer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ressmann
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wagner
authors.forename: Petra
authors.initials: P
authors.lastname: Paul
authors.forename: Manfred
authors.initials: M
authors.lastname: Lehner
authors.forename: Andreas
authors.initials: A
authors.lastname: Heitger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holter
mesh_terms: D000911:Antibodies, Monoclonal; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D016923:Cell Death; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018664:Interleukin-12; D010047:Ovalbumin