title: Vaccination or tolerance to prevent diabetes.
abstract: Experiments with transgenic mice expressing the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promoter (RIP) have demonstrated that potentially self-reactive T cells that normally ignore self peptides may nevertheless be induced by self peptides or "cross-reactive" foreign (e.g. viral) peptides that arise in the host in an immunogenic form; once activated these potentially self-reactive T cells may cause autoaggressive diseases (e.g. diabetes). The possibility of vaccinating against such T cell-mediated immunopathological diseases was evaluated in the RIP-GP transgenic mouse line Bln. Any attempt to vaccinate with the self antigen itself (e.g. recombinant vaccinia virus expressing LCMV-GP) failed to protect mice from disease. However, immunization with a recombinant vaccinia virus expressing LCMV-nucleoprotein (vacc-NP) as a non-GP LCMV vaccine was able to modulate the immune response and prevented autoaggressive disease in a MHC-dependent fashion. In contrast, tolerance induction neonatally or, more generally applicable, by lethal irradiation and reconstitution with neo-self antigen-expressing bone marrow cells always resulted in prevention of virally induced diabetes in this model situation.
authors.affiliation: Department of Pathology, University of Zurich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Oehen
authors.forename: P S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: P
authors.initials: P
authors.lastname: Aichele
authors.forename: K
authors.initials: K
authors.lastname: Bürki
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D006023:Glycoproteins / Q000276:immunology*; D007108:Immune Tolerance; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D006023:Glycoproteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines