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Distinct kinetics and dynamics of cross‐presentation in liver sinusoidal endothelial cells compared to dendritic cells
Author(s) -
Schurich Anna,
Böttcher Jan P.,
Burgdorf Sven,
Penzler Patrick,
Hegenbarth Silke,
Kern Michaela,
Dolf Andreas,
Endl Elmar,
Schultze Joachim,
Wiertz Emmanuel,
Stabenow Dirk,
Kurts Christian,
Knolle Percy
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23075
Subject(s) - cross presentation , antigen presentation , antigen presenting cell , microbiology and biotechnology , antigen , immune system , biology , immunology , dendritic cell , t cell , cd8
Cross‐presentation is an important function of immune competent cells, such as dendritic cells (DCs), macrophages, and an organ‐resident liver cell population, i.e., liver sinusoidal endothelial cells (LSECs). Here, we characterize in direct comparison to DCs the distinct dynamics and kinetics of cross‐presentation employed by LSECs, which promote tolerance induction in CD8 T cells. We found that LSECs were as competent in cross‐presenting circulating soluble antigen ex vivo as DCs at a per‐cell basis. However, antigen uptake in vivo was 100‐fold more pronounced in LSECs, indicating distinct mechanisms of cross‐presentation. In contrast to mannose‐receptor–mediated antigen uptake and routing into stable endosomes dedicated to cross‐presentation in DCs, we observed distinct antigen‐uptake and endosomal routing with high antigen turnover in LSECs that resulted in short‐lived cross‐presentation. Receptor‐mediated endocytosis did not always lead to cross‐presentation, because immune‐complexed antigen taken up by the Fc‐receptor was not cross‐presented by LSECs, indicating that induction of CD8 T cell tolerance by LSECs is impaired in the presence of preexisting immunity. Conclusion: These results provide a mechanistic explanation how organ‐resident LSECs accommodate continuous scavenger function with the capacity to cross‐present circulating antigens using distinct kinetics and dynamics of antigen‐uptake, routing and cross‐presentation compared to DCs. (H EPATOLOGY 2009.)