Impaired antigen presentation by human monocytes during endotoxin tolerance

Endotoxin tolerance (ET) has been described as a temporary alteration in th e 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 initiatio n of the specific immune response as antigen-presenting cells. This study i nvestigated the capacity of human blood monocytes to induce T-cell stimulat ion in ET. First, the expression of monocyte surface molecules, important f or T-cell interaction, was analyzed by flow cytometry. In vitro priming of peripheral blood mononuclear cells with LPS clearly down-regulates major hi stocompatibility 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 accesso ry molecules on monocytes were only marginally down-regulated (CD58), were not significantly changed during ET (CD40), or even remained up regulated a fter initial LPS priming (CD54, CD80). Second, an impact of these phenotypi c alterations on the accessory function of monocytes was observed. This was manifested as diminished T-cell proliferation and interferon (IFN)-gamma r elease in response to the presence of different recall antigens, Neutralizi ng IL-10 during LPS priming prevented the diminished T-cell IFN-gamma produ ction but had little effect on T-cell proliferation. These data confirm tha t ET is an appropriate model of the monocyte functional state in immunopara lysis, which is frequently observed in patients after septic shock, trauma, or major surgery. (Blood. 2000;96:218-223) (C) 2000 by The American Societ y of Hematology.