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

被引：114

作者：

Vezys, V ^{[1
]}

Olson, S ^{[1
]}

Lefrançois, L ^{[1
]}

机构：

[1] Univ Connecticut, Ctr Hlth, Dept Med, Div Rheumat Dis, Farmington, CT 06030 USA

来源：

IMMUNITY | 2000年 / 12卷 / 05期

关键词：

D O I：

10.1016/S1074-7613(00)80202-2

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 lytic 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.

引用

页码：505 / 514

页数：10

共 54 条

[1] CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells [J].