title: Global Inhibition of DC Priming Capacity in the Spleen of Self-Antigen Vaccinated Mice Requires IL-10.
abstract: Dendritic cells (DC) in the spleen are highly activated following intravenous vaccination with a foreign-antigen, promoting expansion of effector T cells, but remain phenotypically and functionally immature after vaccination with a self-antigen. Up-regulation or suppression of expression of a cohort of pancreatic enzymes 24-72 h post-vaccination can be used as a biomarker of stimulatory versus tolerogenic DC, respectively. Here we show, using MUC1 transgenic mice and a vaccine based on the MUC1 peptide, which these mice perceive as a self-antigen, that the difference in enzyme expression that predicts whether DC will promote immune response or immune tolerance is seen as early as 4-8 h following vaccination. We also identify early production of IL-10 as a predominant factor that both correlates with this early-time point and controls DC function. Pre-treating mice with an antibody against the IL-10 receptor prior to vaccination results in DC that up-regulate CD40, CD80, and CD86 and promote stronger IFNγ+ T cell responses. This study suggests that transient inhibition of IL-10 prior to vaccination could improve responses to cancer vaccines that utilize self-tumor antigens.
authors.affiliation: Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA , USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Marvel
authors.affiliation: Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA , USA.
authors.forename: Olivera J
authors.initials: OJ
authors.lastname: Finn
keywords: IL-10; MUC1; T cell response; cancer vaccine; dendritic cells