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-gamma, 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. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.