Abstracts (complete list) - Wissenschaft Online

Anna Schurich, Silke Hegenbarth, Jan Böttcher, Sven Burgdorf, Andreas Dolf, Elmar
Endl, Christian Kurts, Percy A. Knolle
Liver sinusoidal endothelial cells are more efficient in crosspresentation
than CD8alpha splenic dendritic cells expressing
endocytic receptors devoted to cross-presentation
Liver sinusoidal endothelial cells (LSEC) constitute a unique antigen presenting cell
population. LSEC efficiently take up and cross-present antigen to naïve CD8 T-cells
inducing T-cell tolerance. In order to unambiguously investigate and compare crosspresentation
in LSEC to conventional APC such as DCs we developed a new isolation
method that involves functional identification of LSEC in vivo via their extraordinary
scavenger activity and fluorescence activated cell sorting. This method yielded highly
pure cell populations (≥ 99.9 %) for functional analysis ex vivo. We compared the
efficiency of isolated LSEC and splenic DCs for cross-presentation of ovalbumin to CD8
T- cells ex vivo one hour after intravenous antigen injection. LSEC were more efficient
in cross-presentation on a per cell basis than CD8α positive splenic DCs. However,
antigen was not retained in LSEC in vivo, because 90% of antigen was lost after 24h
and cross-presentation decreased correspondingly. In contrast less efficient crosspresentation
by DCs was maintained over 24h. It was recently shown that crosspresentation
of soluble exogenous ovalbumin in DCs is determined by the receptor used
for endocytosis: the mannose receptor (MR) routing ovalbumin into cross-presentation
and scavenger receptors into MHC II restricted presentation. We found that MR cell
surface expression was higher in LSEC than in DCs. MR -/- LSEC, in contrast to DC, do
not rely exclusively on the MR, but were still capable of cross-presenting ovalbumin
indicating expression of another receptor involved in cross-presentation. Further
experiments will characterise this receptor.
Collectively our data show that LSEC are more efficient than CD8&alpha positive DC in
cross-presentation of soluble exogenous ovalbumin, utilising endocytic receptors
devoted to cross-presentation.