title: Cross-presentation of antigen by diverse subsets of murine liver cells.
abstract: Antigen cross-presentation is a principal function of specialized antigen-presenting cells of bone marrow origin such as dendritic cells. Although these cells are sometimes known as "professional" antigen-presenting cells, nonbone marrow-derived cells may also act as antigen-presenting cells. Here, using four-way liver cell isolation and parallel comparison of candidate antigen-presenting cells, we show that, depending on the abundance of antigen-donor cells, different subsets of liver cells could cross-present a hepatocyte-associated antigen. This function was observed in both liver sinusoidal endothelial cells and Kupffer cells even at very low antigen concentration, as well as when using soluble protein. Antigen cross-presentation by liver cells induced efficient CD8+ T-cell proliferation in a similar manner to classical dendritic cells from spleen. However, proliferated cells expressed a lower level of T-cell activation markers and intracellular interferon-gamma levels. In contrast to classical spleen dendritic cells, cross-presentation by liver antigen-presenting cells was predominantly dependent on intercellular adhesion molecule-1.
  
  
  CONCLUSIONS
  Hepatic sinusoids are an environment rich in antigen cross-presenting activity. However, the liver's resident antigen-presenting cells cause partial T-cell activation. These results clarify how the liver can act as a primary site of CD8+ T-cell activation, and why immunity against hepatocyte pathogens is sometimes ineffective.
authors: Malaria Program, Seattle Biomedical Research Institute, Seattle, WA, USA. ebrahimkhani.m@gmail.com
authors: Mohammad R
authors: MR
authors: Ebrahimkhani
authors: Isaac
authors: I
authors: Mohar
authors: Ian N
authors: IN
authors: Crispe
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D022781:Hepatocytes / Q000166:cytology / Q000382:microbiology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008107:Liver Diseases / Q000276:immunology / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012680:Sensitivity and Specificity
chemical_list: D018799:Intercellular Adhesion Molecule-1