Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity.
OBJECTIVE
Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8(+) T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8(+) T-cell activation upon such stimulation.


METHODS
Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo relevance of the findings was confirmed with bone-marrow chimeric animals.


RESULTS
LSECs expressed numerous pattern recognition receptors that allowed for sentinel function, but ligand-induced activation of these receptors was not sufficient to overcome tolerance induction of CD8(+) T cells. Importantly, viral infection with murine cytomegalovirus caused functional maturation of antigen-presenting LSECs and was sufficient to promote antigen-specific differentiation into effector CD8(+) T cells in the absence of dendritic cells and independent of CD80/86.


CONCLUSIONS
These results shed new light on the generation of organ-specific immunity and may contribute to overcoming tolerance in relevant situations, such as cancer.
Kern
Michaela
M
Institute of Molecular Medicine, University of Bonn, Bonn, Germany.
Popov
Alexey
A
Scholz
Kai
K
Schumak
Beatrix
B
Djandji
Dominik
D
Limmer
Andreas
A
Eggle
Daniela
D
Sacher
Torsten
T
Zawatzky
Rainer
R
Holtappels
Rafaela
R
Reddehase
Matthias J
MJ
Hartmann
Gunther
G
Debey-Pascher
Svenja
S
Diehl
Linda
L
Kalinke
Ulrich
U
Koszinowski
Ulrich
U
Schultze
Joachim
J
Knolle
Percy A
PA
D019264:Adoptive Transfer; D000818:Animals; D001853:Bone Marrow; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002678:Chimera; D042783:Endothelial Cells / Q000166:cytology / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000821:virology*; D051379:Mice; D018146:Muromegalovirus; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D008024:Ligands; D051192:Receptors, Pattern Recognition