Abstracts (complete list) - Wissenschaft Online

Nanette von Oppen, Linda Diehl, Rene Tolba, Percy Knolle
CROSS-PRESENTING LIVER SINUSOIDAL ENDOTHELIAL CELLS
ESTABLISH ANTIGEN-SPECIFIC ADHESION OF NAÏVE CD8 T
CELLS LEADING TO T CELL TOLERANCE IN VIVO
Presentation of antigen in the liver leads to induction of T cell tolerance rather than
immunity. The ability of liver sinusoidal endothelial cells (LSEC) to cross-present
exogenous antigens on MHC I molecules to naïve CD8 T cells and to induce CD8 T cell
tolerance contributes to the hepatic immune regulatory function. However, the
mechanisms underlying recruitment of naïve CD8 T cells to the liver remained unclear.
We provide evidence that organ-resident cross-presenting liver sinusoidal endothelial
cells recruit naïve CD8 T cells antigen-specifically to the liver. Antigen-specific hepatic
recruitment of naïve CD8 T cells occurred rapidly within 4 hours after antigen-challenge
and was exclusively observed in the liver but not in spleen, lymph nodes or lung.
Expression of CD54 supported antigen-specific T cell adhesion but was not essential.
Antigen-specific adhesion was accompanied by rapid stimulation of T cells, as shown by
up-regulation of CD69, which was also predominantly observed in the liver. Experiments
employing bone marrow chimeric mice unequivocally demonstrated that organ-resident
but not myeloid APC were responsible for antigen-specific naïve T cell adhesion.
Importantly adhesion of naïve CD8 T cells to cross-presenting LSEC in bone marrow
chimeric mice resulted in tolerance of these cells. Our data attribute a novel function to
LSEC, i.e. antigen-specific retention of naïve CD8 T cells, which is not observed for
other organs. Delivery of a flow-stop signal by tolerogenic LSEC to passenger naïve CD8
T cells in the hepatic circulation provides a mechanistic insight into the early steps of
induction of CD8 T cell tolerance in the liver.