title: Impaired antigen presentation by human monocytes during endotoxin tolerance.
abstract: Endotoxin tolerance (ET) has been described as a temporary alteration in the lipopolysaccharide (LPS) response of monocytic cells after an initial LPS exposure with respect to the production of soluble immunomodulators. Apart from the LPS response, monocytic cells play an important role in initiation of the specific immune response as antigen-presenting cells. This study investigated the capacity of human blood monocytes to induce T-cell stimulation in ET. First, the expression of monocyte surface molecules, important for T-cell interaction, was analyzed by flow cytometry. In vitro priming of peripheral blood mononuclear cells with LPS clearly down-regulates major histocompatibility complex class II molecules and the costimulatory molecule CD86. Both changes were dependent on the endogenous interleukin (IL)-10 and less so on the transforming growth factor-beta. In contrast, other accessory molecules on monocytes were only marginally down-regulated (CD58), were not significantly changed during ET (CD40), or even remained up-regulated after initial LPS priming (CD54, CD80). Second, an impact of these phenotypic alterations on the accessory function of monocytes was observed. This was manifested as diminished T-cell proliferation and interferon (IFN)-gamma release in response to the presence of different recall antigens. Neutralizing IL-10 during LPS priming prevented the diminished T-cell IFN-gamma production but had little effect on T-cell proliferation. These data confirm that ET is an appropriate model of the monocyte functional state in immunoparalysis, which is frequently observed in patients after septic shock, trauma, or major surgery.
authors.affiliation: Institute of Medical Immunology, Medical School Charité, Humboldt University, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wolk
authors.forename: W D
authors.initials: WD
authors.lastname: Döcke
authors.forename: V
authors.initials: V
authors.lastname: von Baehr
authors.forename: H D
authors.initials: HD
authors.lastname: Volk
authors.forename: R
authors.initials: R
authors.lastname: Sabat
mesh_terms: D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D002478:Cells, Cultured; D004926:Escherichia coli; D006684:HLA-DR Antigens / Q000097:blood / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma