Involvement of the Liver in the Induction of CD8 T Cell Tolerance towards Oral Antigen

Zusammenfassung

Die Leber ist ein Organ mit einzigartigem immunregulatorischen Potenzial. In dieser Arbeit wird die experimentelle Evidenz dargestellt, die für die Beteiligung hepatischer Zellpopulationen an der Induktion von oraler Toleranz spricht. Obwohl die Induktion von Immuntoleranz gegenüber oralen Antigenen vor allem im lymphatischen Gewebe des Gastrointestinaltraktes erfolgt, besteht ein weiterer Bedarf für die Aufrechterhaltung peripherer Immuntoleranz außerhalb des Gastrointestinaltraktes, da orale Antigene innerhalb von Minuten nach Aufnahme schnell über den Blutstrom systemisch verteilt werden. Neben hepatischen dendritischen Zellen sind vor allem sinusoidale Endothelzellen der Leber an der Aufnahme von oralem Antigen aus portalvenösem Blut und der Kreuzpräsentation dieser Antigene auf MHC-I-Molekülen für CD8-T-Zellen beteiligt. Die Folge der Kreuzpräsentation oraler Antigene durch sinusoidale Endothelzellen der Leber ist die Induktion von CD8-T-Zell-Immuntoleranz. Diese Befunde unterstreichen die Bedeutung der Leber in der Aufrechterhaltung peripherer Immuntoleranz auch gegenüber oralen Antigenen.

Abstract

The liver is an organ with unique immune regulatory potential. This review highlights the experimental evidence for the involvement of hepatic cell populations in the induction of oral tolerance. Although immune tolerance towards oral antigens is mainly induced in the gastrointestinal tract within gut associated lymphatic tissue via generation of regulatory CD4 T cells, there is a further need for tolerance induction outside the gastrointestinal tract, because oral antigens rapidly distribute within minutes systemically through the blood stream. Besides hepatic dendritic cells, liver sinusoidal endothelial cells are active in the uptake and cross-presentation of oral antigens from portal venous blood and engage in the induction of CD8 T cell tolerance towards these antigens. These reports strengthen the notion that the liver participates in the induction of oral tolerance.

Schlüsselwörter

Sinusoidale Endothelzellen der Leber - hepatische dendritische Zellen - Antigenaufnahme - Kreuzpräsentation - Immuntoleranz

Key words

Liver sinusoidal endothelial cells - hepatic dendritic cells - antigen uptake - cross-presentation - immune tolerance

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