We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses.
- Authors
Felzmann, Thomas; Hüttner, Katharina; Breuer, Sabine; Wimmer, Doris; Ressmann, Gabriele; Wagner, Dagmar; Paul, Petra; Lehner, Manfred; Heitger, Andreas; Holter, Wolfgang
- 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.
- Subjects
DENDRITIC cells; ANTIGEN presenting cells; LYMPHOID tissue; INTERLEUKIN-12; INTERLEUKINS; ANTIGENS; IMMUNE response; IMMUNOLOGY
- Publication
Cancer Immunology, Immunotherapy, 2005, Vol 54, Issue 8, p769
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-004-0637-2