title: Cutting Edge: Nonobese Diabetic Mice Deficient in Chromogranin A Are Protected from Autoimmune Diabetes.
abstract: T cells reactive to β cell Ags are critical players in the development of autoimmune type 1 diabetes. Using a panel of diabetogenic CD4 T cell clones derived from the NOD mouse, we recently identified the β cell secretory granule protein, chromogranin A (ChgA), as a new autoantigen in type 1 diabetes. CD4 T cells reactive to ChgA are pathogenic and rapidly transfer diabetes into young NOD recipients. We report in this article that NOD.ChgA(-/-) mice do not develop diabetes and show little evidence of autoimmunity in the pancreatic islets. Using tetramer analysis, we demonstrate that ChgA-reactive T cells are present in these mice but remain naive. In contrast, in NOD.ChgA(+/+) mice, a majority of the ChgA-reactive T cells are Ag experienced. Our results suggest that the presence of ChgA and subsequent activation of ChgA-reactive T cells are essential for the initiation and development of autoimmune diabetes in NOD mice.
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO 80045; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
authors.forename: Rocky L
authors.initials: RL
authors.lastname: Baker
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO 80045; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
authors.forename: Brenda
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO 80045; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Wiles
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO 80045; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
authors.forename: Robin S
authors.identifier: http://orcid.org/0000-0001-7867-8653
authors.initials: RS
authors.lastname: Lindsay
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO 80045; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
authors.forename: Gene
authors.initials: G
authors.lastname: Barbour
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO 80045; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
authors.forename: Thomas
authors.initials: T
authors.lastname: Delong
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO 80045; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Friedman
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO 80045; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206 Katie.Haskins@ucdenver.edu.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Haskins
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D053379:Chromogranin A / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D018895:Microsatellite Repeats / Q000235:genetics
chemical_list: D001324:Autoantigens; D053379:Chromogranin A; C506155:chromogranin A, mouse