Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses
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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.
KeywordsIL-12 Dendritic cells Antigene Immune response
This work was supported by numerous private donations to the Children’s Cancer Research Institute, Vienna, Austria that partly funded this study, and by grants from the Austrian Industrial Research Promotion Fund (Forschungsförderungsfond der Gewerblichen Wirtschaft, Projektnummer 804445) and from the Vienna Business Agency (Wiener Wirtschaftsförderungsfond).
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