title: 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.
authors.affiliation: Department of Rheumatology and Inflammation Research, Göteborg University, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Ostman
authors.forename: Maria
authors.initials: M
authors.lastname: Taube
authors.forename: Esbjörn
authors.initials: E
authors.lastname: Telemo
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D022162:Cytoplasmic Vesicles / Q000276:immunology* / Q000648:ultrastructure; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D010047:Ovalbumin