Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance.

Abstract:

:After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver sinusoidal endothelial cells (LSEC) eliminate blood-borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Oral antigens were efficiently cross-presented on H-2K(b) by LSEC to naive CD8 T cells. Cross-presentation efficiency in LSEC but not dendritic cells was increased by antigen-exposure to heat or low pH. Mechanistically, cross-presentation in LSEC requires endosomal maturation, involves hsc73 and proteasomal degradation. H-2K(b)-restricted cross-presentation of oral antigens by LSEC in vivo induced CD8 T cell priming and led to development of CD8 T cell tolerance in two independent experimental systems. Adoptive transfer of LSEC from mice fed with antigen (ovalbumin) into RAG2-/- knockout mice, previously reconstituted with naive ovalbumin-specific CD8 T cells, prevented development of specific cytotoxicity and expression of IFN-gamma in CD8 T cells. Using a new transgenic mouse line expressing H-2K(b) only on endothelial cells, we have demonstrated that oral antigen administration leads to tolerance in H-2K(b)-restricted CD8 T cells. Collectively, our data demonstrate a participation of the liver, in particular scavenger LSEC, in development of CD8 T cell tolerance towards oral antigens.

journal_name

Eur J Immunol

authors

Limmer A,Ohl J,Wingender G,Berg M,Jüngerkes F,Schumak B,Djandji D,Scholz K,Klevenz A,Hegenbarth S,Momburg F,Hämmerling GJ,Arnold B,Knolle PA

doi

10.1002/eji.200526034

keywords:

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

2970-81

issue

10

eissn

0014-2980

issn

1521-4141

journal_volume

35

pub_type

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