title: Checkpoints in the progression of autoimmune disease: lessons from diabetes models.
abstract: In the last few years, data from experiments employing transgenic models of autoimmune disease have strengthened a particular concept of autoimmunity: disease results not so much from cracks in tolerance induction systems, leading to the generation of anti-self repertoire, as from the breakdown of secondary systems that keep these cells in check. T cells with anti-self specificities are readily found in disease-free individuals but ignore target tissues. This is also the case in some transgenic models, in spite of overwhelming numbers of autoreactive cells. In other instances, local infiltration and inflammation result, but they are well tolerated for long periods of time and do not terminally destroy target tissue. We review the possible molecular and cellular mechanisms that underlie these situations, with a particular emphasis on the destruction of pancreatic beta cells in transgenic models of insulin-dependent disease.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, Strasbourg, France.
authors.forename: I
authors.initials: I
authors.lastname: André
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Katz
authors.forename: C
authors.initials: C
authors.lastname: Benoist
authors.forename: D
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell