title: Antigen recognition in the islets changes with progression of autoimmune islet infiltration.
abstract: In type 1 diabetes, the pancreatic islets are an important site for therapeutic intervention because immune infiltration of the islets is well established at diagnosis. Therefore, understanding the events that underlie the continued progression of the autoimmune response and islet destruction is critical. Islet infiltration and destruction is an asynchronous process, making it important to analyze the disease process on a single islet basis. To understand how T cell stimulation evolves through the process of islet infiltration, we analyzed the dynamics of T cell movement and interactions within individual islets of spontaneously autoimmune NOD mice. Using both intravital and explanted two-photon islet imaging, we defined a correlation between increased islet infiltration and increased T cell motility. Early T cell arrest was Ag dependent and due, at least in part, to Ag recognition through sustained interactions with CD11c(+) APCs. As islet infiltration progressed, T cell motility became Ag independent, with a loss of T cell arrest and sustained interactions with CD11c(+) APCs. These studies suggest that the autoimmune T cell response in the islets may be temporarily dampened during the course of islet infiltration and disease progression.
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, CO 80206;
authors.forename: Robin S
authors.initials: RS
authors.lastname: Lindsay
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143; and.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Corbin
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, CA 94143.
authors.forename: Ashley
authors.initials: A
authors.lastname: Mahne
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Bonnie E
authors.initials: BE
authors.lastname: Levitt
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gebert
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Wigton
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, CO 80206;
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Bradley
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, CO 80206;
authors.forename: Kathryn
authors.initials: K
authors.lastname: Haskins
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, CO 80206;
authors.forename: Jordan
authors.initials: J
authors.lastname: Jacobelli
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, CA 94143.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143; and.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, CO 80206; FriedmanR@NJHealth.org.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Friedman
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000473:pathology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D001324:Autoantigens; D039521:CD11c Antigen