title: Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice.
abstract: To address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP) in the beta islet cells of the pancreas. The fate of LCMV GP-specific T cells was followed by breeding the GP transgenic mice with T cell receptor transgenic mice, specific for LCMV and H-2Db. These studies suggest that "peripheral tolerance" of self-reactive T cells does not involve clonal deletion, clonal anergy, or a decrease in the density of T cell receptors or accessory molecules. Instead, this model indicates that self-reactive cytotoxic T cells may remain functionally unresponsive, owing to a lack of appropriate T cell activation. Infection of transgenic mice with LCMV readily abolishes peripheral unresponsiveness to the self LCMV GP antigen, resulting in a CD8+ T cell-mediated diabetes. These data suggest that similar mechanisms may operate in several so-called "T cell-mediated autoimmune diseases."
authors.affiliation: Department of Experimental Pathology, University Hospital, Zurich, Switzerland.
authors.forename: P S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: S
authors.initials: S
authors.lastname: Oehen
authors.forename: K
authors.initials: K
authors.lastname: Buerki
authors.forename: H
authors.initials: H
authors.lastname: Pircher
authors.forename: C T
authors.initials: CT
authors.lastname: Ohashi
authors.forename: B
authors.initials: B
authors.lastname: Odermatt
authors.forename: B
authors.initials: B
authors.lastname: Malissen
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis / Q000235:genetics*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D007108:Immune Tolerance / Q000235:genetics*; D016219:Immunotherapy, Adoptive; D007328:Insulin / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D007515:Islets of Langerhans / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; D006023:Glycoproteins; D007328:Insulin; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D014764:Viral Proteins; D007371:Interferon-gamma