The role of hepatic immune regulation in systemic immunity to viral infection View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-02

AUTHORS

Percy A. Knolle, Jan Böttcher, Li-Rung Huang

ABSTRACT

The liver has particular immune functions attributed by its unique microenvironment and its liver-resident cell populations. During autoimmunity and viral hepatitis, the liver serves as target for effector responses of immune cells. However, skewing of effector T cell functions through tolerogenic liver-resident antigen-presenting cells and through the immune regulatory hepatic microenvironment. Importantly, the liver also participates in shaping systemic antigen-specific immunity. Local antigen-presenting cell populations, in particular liver sinusoidal endothelial cells (LSECs), cross-present soluble, circulating or hepatocyte-derived antigens to naïve CD8 T cells. Upon priming by cross-presenting LSECs, naïve CD8 T cells develop into a unique population of antigen-experienced memory-like T cell population that can be reactivated in an inflammatory context to protect against infection with viruses or bacteria. Furthermore, upon prolonged inflammatory TNF-dependent signaling, the induction of intrahepatic myeloid cell aggregates for T cell population expansion (iMATEs) is observed in liver tissue. iMATEs are formed by inflammatory monocytes developing into dendritic cells and function to attract recently activated CD8 T cells. Those CD8 T cells located within the cocoon-like iMATE structure show strong proliferation initiated by co-stimulatory signaling. Locally expanded CD8 T cells are key to control acute and chronic viral infections. The mechanistic understanding of local hepatic T cell priming and local expansion of effector CD8 T cells will help to develop novel therapeutic vaccination strategies. More... »

PAGES

21-27

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00430-014-0371-0

DOI

http://dx.doi.org/10.1007/s00430-014-0371-0

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25523194


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53 schema:description The liver has particular immune functions attributed by its unique microenvironment and its liver-resident cell populations. During autoimmunity and viral hepatitis, the liver serves as target for effector responses of immune cells. However, skewing of effector T cell functions through tolerogenic liver-resident antigen-presenting cells and through the immune regulatory hepatic microenvironment. Importantly, the liver also participates in shaping systemic antigen-specific immunity. Local antigen-presenting cell populations, in particular liver sinusoidal endothelial cells (LSECs), cross-present soluble, circulating or hepatocyte-derived antigens to naïve CD8 T cells. Upon priming by cross-presenting LSECs, naïve CD8 T cells develop into a unique population of antigen-experienced memory-like T cell population that can be reactivated in an inflammatory context to protect against infection with viruses or bacteria. Furthermore, upon prolonged inflammatory TNF-dependent signaling, the induction of intrahepatic myeloid cell aggregates for T cell population expansion (iMATEs) is observed in liver tissue. iMATEs are formed by inflammatory monocytes developing into dendritic cells and function to attract recently activated CD8 T cells. Those CD8 T cells located within the cocoon-like iMATE structure show strong proliferation initiated by co-stimulatory signaling. Locally expanded CD8 T cells are key to control acute and chronic viral infections. The mechanistic understanding of local hepatic T cell priming and local expansion of effector CD8 T cells will help to develop novel therapeutic vaccination strategies.
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