Expression of intestine-specific antigen reveals novel pathways of CD8 T cell tolerance induction

Vaiva Vezys, Sara Olson, Leo Lefrançois

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Reactivity to intestinal epithelium-specific antigen was studied by transgenic expression of cytosolic ovalbumin controlled by an enterocyte-specific promoter. Transferred OVA-specific CD8 cells (OT-I) preferentially expanded in mucosal lymphoid tissues and the epithelium but failed to cause tissue damage. In contrast, concomitant VSV-ova infection induced OT-I-mediated epithelial cell destruction that correlated with antigen density. OT-I cells retained in the epithelium exhibited high levels of lyric activity but were unable to produce cytokines. The mice were systemically tolerant to OVA since endogenous CD8 cells were nonresponsive to VSV-ova infection. Thus, intestinal antigen gained access to peripheral tissues via absorption from effete epithelial cells. This system demonstrated a requirement for inflammation to drive pathogenic autoreactivity against enterocytes and identified pathways of intestine-specific immunoregulation.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalImmunity
Volume12
Issue number5
DOIs
StatePublished - 2000

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