Induction of cytokine production and proliferation of memory lymphocytes by murine liver dendritic cell progenitors: role of these progenitors as immunogenic resident antigen-presenting cells in the liver

Background/Aims: Many pathogenic organisms, including hepatotrophic viruses enter the liver and induce an immune response, but there is little information about the immunogenic resident antigen-presenting cells. The aim of this study was to determine whether dendritic cells in the liver are immunogenic antigen-presenting cells. Methods: Liver dendritic cell progenitors were enriched from normal C57BL/6 mice by culturing non-parenchymal cells with granulocyte–macrophage colony stimulating factor for 7 days. Then the surface antigen (MHC class II, CD86) expression, endocytic capacity, ability to induce cytokines, and the proliferation of memory lymphocytes were investigated. Results: Freshly enriched liver dendritic cell progenitors exhibited an immature phenotype and failed to stimulate allogenic T cells. However, the progenitors underwent maturation following exposure to antigens such as hepatitis B surface antigen and keyhole limpet hemocyanin. The progenitors then became strong stimulators of allogenic T cells, supported the production of interleukin-12 and interferon-γ, and induced the proliferation of antigen-specific memory lymphocytes. Conclusions: Dendritic cell progenitors are immunogenic resident antigen-presenting cells in the liver. Simultaneous investigation of both tolerogenic and immunogenic resident antigen-presenting cells may provide insights into the pathogenesis of persistent infection and autoimmmune diseases of the liver.