title: Breaking self-tolerance in nonobese diabetic mice.
abstract: Unresponsiveness to self is maintained through two mechanisms of immune regulation: thymic-negative selection and peripheral tolerance. Although thymic-negative selection is a major mechanism to eliminate self-reactive T cells, normal mice have readily detectable populations of T cells reactive to self-proteins but do not exhibit autoimmune responses. It has been postulated that autoimmune disease results from breakdown or loss of peripheral tolerance. We present data that demonstrate that peripheral tolerance or unresponsiveness to self can be broken in nonobese diabetic (NOD) mice. Immunization of NOD mice (but not of conventional mice) with self-peptides caused an immune response to self-peptide with resultant autoproliferation of peripheral lymphocytes. Autoproliferation of self-reactive T cells in NOD mice resulted from the recognition and proliferation of the activated T cells to endogenously processed and presented self-antigens. This loss of self-tolerance demonstrated in vitro may well be the basis of NOD autoimmune disease in vivo.
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, California 94305, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Ridgway
authors.forename: M
authors.initials: M
authors.lastname: Fassò
authors.forename: A
authors.initials: A
authors.lastname: Lanctot
authors.forename: C
authors.initials: C
authors.lastname: Garvey
authors.forename: C G
authors.initials: CG
authors.lastname: Fathman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD / Q000276:immunology*; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D013045:Species Specificity
chemical_list: D000949:Histocompatibility Antigens Class II; D009211:Myoglobin; D010446:Peptide Fragments