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Uptake of microparticle‐adsorbed protein antigen by bone marrow‐derived dendritic cells results in up‐regulation of interleukin‐1α and interleukin‐12 p40/p35 and triggers prolonged, efficient antigen presentation

作者:Christoph Scheicher, Maria Mehlig, Hans‐Peter Dienes, Konrad Reske · 发表于:European Journal of Immunology · 年份:1995 · DOI:10.1002/eji.1830250615 · 被引用次数:100 · 研究领域:Immunotherapy and Immune Responses、T-cell and B-cell Immunology、vaccines and immunoinformatics approaches

Dendritic cells synthesize and express major histocompatibility complex (MHC) class II peptide-binding elements constitutively and, therefore, belong to the category of professional antigen-presenting cells. Unlike other cells that show constitutive class II expression, such as B cells and certain T cell clones, dendritic cells possess the unique capacity to activate naive T cells. Using dendritic cells generated in vitro by culture of mouse bone marrow in the presence of low doses of recombinant mouse granulocyte/macrophage colony-stimulating factor, we found that discrete maturation stages of these cells can be distinguished which were correlated with defined functional capabilities. The striking observation was the presence of a progenitor dendritic cell expressing low levels of class II which, unlike its differentiated counterpart in vitro, possessed pronounced phagocytic activity. Adding protein antigen to dendritic cells in a particle-adsorbed form, as compared to a soluble form, we demonstrate that phagocytosis of the particle-adsorbed protein by progenitor dendritic cells involves an activation event. This is evidenced by the de novo synthesis of transcripts of interleukin-1 alpha and interleukin-12 p40/p35 as well as transcripts of MHC class II. Most importantly, an augmented and prolonged antigen-presentation capacity was observed when the antigen was given in particle-adsorbed instead of soluble form. These findings indicate that progenitor dendritic cells are func...