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Gastroenterology. 2010 Jan;138(1):336-46. doi: 10.1053/j.gastro.2009.08.057. Epub 2009 Sep 6.

Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity.

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  • 1Institute of Molecular Medicine, University of Bonn, Bonn, Germany.

Abstract

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.

Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID:
19737567
[PubMed - indexed for MEDLINE]
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