On the various manifestations of spontaneous autoimmune diabetes in rodent models.
Autoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares several features, including T lymphocyte infiltration into pancreatic islets and a dependence on permissive class II major histocompatibility complex (MHC) alleles. We report here on an experimental model involving mice that express influenza hemagglutinin (HA) under the control of the insulin promoter and, at the same time, a transgenic class II MHC-restricted T cell receptor (TcR) specific for an HA peptide. These mice spontaneously develop islet infiltrates resembling those found in NOD mice and most animals become diabetic within 8 weeks of age. Because of the availability of a clonotypic TcR antibody, we can be confident that the Ins-HA transgene does not induce any measurable alterations in the vast majority of T cells with the transgenic TcR in primary and secondary lymphoid organs. Continuous export of large numbers of HA-specific lymphocytes from the thymus was not required for the manifestation of the disease since mice thymectomized at 3 days after birth still developed the disease albeit with smaller infiltrates.
Degermann
S
S
Department of Immunology, IMM-16, Scripps Research Institute, La Jolla, CA 92037.
Reilly
C
C
Scott
B
B
Ogata
L
L
von Boehmer
H
H
Lo
D
D
D000818:Animals; D001324:Autoantigens; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology*; D000939:Epitopes; D015870:Gene Expression; D006389:Hemagglutinins, Viral / Q000276:immunology; D007111:Immunity, Cellular; D007328:Insulin / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D001324:Autoantigens; D000939:Epitopes; D006389:Hemagglutinins, Viral; D007328:Insulin; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins