Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity
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Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity. / Kern, Michaela; Popov, Alexey; Scholz, Kai; Schumak, Beatrix; Djandji, Dominik; Limmer, Andreas; Eggle, Daniela; Sacher, Torsten; Zawatzky, Rainer; Holtappels, Rafaela; Reddehase, Matthias J; Hartmann, Gunther; Debey-Pascher, Svenja; Diehl, Linda; Kalinke, Ulrich; Koszinowski, Ulrich; Schultze, Joachim; Knolle, Percy A.
in: GASTROENTEROLOGY, Jahrgang 138, Nr. 1, 01.2010, S. 336-46.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity
AU - Kern, Michaela
AU - Popov, Alexey
AU - Scholz, Kai
AU - Schumak, Beatrix
AU - Djandji, Dominik
AU - Limmer, Andreas
AU - Eggle, Daniela
AU - Sacher, Torsten
AU - Zawatzky, Rainer
AU - Holtappels, Rafaela
AU - Reddehase, Matthias J
AU - Hartmann, Gunther
AU - Debey-Pascher, Svenja
AU - Diehl, Linda
AU - Kalinke, Ulrich
AU - Koszinowski, Ulrich
AU - Schultze, Joachim
AU - Knolle, Percy A
N1 - Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PY - 2010/1
Y1 - 2010/1
N2 - BACKGROUND & AIMS: 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.
AB - BACKGROUND & AIMS: 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.
KW - Adoptive Transfer
KW - Animals
KW - Bone Marrow
KW - CD8-Positive T-Lymphocytes
KW - Cell Differentiation
KW - Cells, Cultured
KW - Chimera
KW - Endothelial Cells
KW - Herpesviridae Infections
KW - Immune Tolerance
KW - Ligands
KW - Liver
KW - Mice
KW - Muromegalovirus
KW - Oligonucleotide Array Sequence Analysis
KW - Organ Specificity
KW - Receptors, Pattern Recognition
U2 - 10.1053/j.gastro.2009.08.057
DO - 10.1053/j.gastro.2009.08.057
M3 - SCORING: Journal article
C2 - 19737567
VL - 138
SP - 336
EP - 346
JO - GASTROENTEROLOGY
JF - GASTROENTEROLOGY
SN - 0016-5085
IS - 1
ER -