Following a diabetogenic T cell from genesis through pathogenesis.
Nonobese diabetic (NOD) mice spontaneously develop a disease very similar to type 1 diabetes in humans. We have generated a transgenic mouse strain carrying the rearranged T cell receptor genes from a diabetogenic T cell clone derived from a NOD mouse. Self-reactive T cells expressing the transgene-encoded specificity are not tolerized in these animals, resulting in rampant insulitis and eventually diabetes. Features of the disease process emphasize two so-called check-points, recognized previously in the NOD and human diseases but easily misinterpreted. Although NOD mice are protected from insulitis and diabetes by expression of the E molecule encoded in the major histocompatibility complex, the transgenics are not, permitting us to exclude some possible mechanisms of protection.
Katz
J D
JD
Laboratoire de Génétique Moléculaire des Eucaryotes Centre National de la Recherche Scientifique Unité 184 de Biologie Moléculaire l'Institut National de la Santé et de la Recherche Médicale.
Wang
B
B
Haskins
K
K
Benoist
C
C
Mathis
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D013363:Submandibular Gland / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D009838:Oligodeoxyribonucleotides; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta