Tolerosome-induced Oral Tolerance Is MHC Dependent

Immunology. 2005 Dec;116(4):464-76. doi: 10.1111/j.1365-2567.2005.02245.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adoptive Transfer
  • Animals
  • Antigen-Presenting Cells / immunology
  • Cytoplasmic Vesicles / immunology*
  • Cytoplasmic Vesicles / ultrastructure
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism*
  • Immune Tolerance*
  • Immunity, Mucosal
  • Immunoenzyme Techniques
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Intestinal Mucosa / immunology
  • Intestine, Small / immunology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, SCID
  • Ovalbumin / immunology
  • Spleen / immunology
  • T-Lymphocytes / immunology

Substances

  • Histocompatibility Antigens Class II
  • Interferon-gamma
  • Ovalbumin