Tolerosome-induced oral tolerance is MHC dependent.

Abstract:

:Oral administration of a protein antigen generates a serum factor that induces tolerance when transferred into naïve recipients. This serum factor has been described in rats as consisting of exosome-like structures or tolerosomes, which express major histocompatibility complex class II molecules (MHCII) and mediate antigen-specific tolerance. In this study, we investigated the functions of serum-derived tolerosomes both in vivo and in vitro. Tolerosomes were purified from the 100,000 g pellet fraction of serum from ovalbumin (OVA)-fed mice. When transferred into naïve recipient mice, the tolerosomes mediated OVA-specific tolerance. We also found that tolerosomes from OVA-fed mice induced the activation of OVA-specific T cells both in vivo and in vitro. The inoculation of severe combined immunodeficiency (SCID) mice with an interferon-gamma-producing cell line normalized the expression of MHCII in the intestinal epithelial cells and restored their ability to generate tolerosomes. Syngeneic but not allogeneic transfer of tolerosomes from OVA-fed donors induced tolerance in the recipients. Our results show that tolerosomes can be isolated from mouse serum, that tolerosome-induced oral tolerance requires MHCII expression in intestinal epithelial cells, and that tolerosomes are functional only in syngeneic recipients.

journal_name

Immunology

journal_title

Immunology

authors

Ostman S,Taube M,Telemo E

doi

10.1111/j.1365-2567.2005.02245.x

keywords:

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

464-76

issue

4

eissn

0019-2805

issn

1365-2567

pii

IMM2245

journal_volume

116

pub_type

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