title: Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular response.
abstract: In an accompanying paper, we find specific localization of diabetogenic T cells only to islets of Langerhans bearing the specific antigen. Instrumental in the specific localization was the presence of intraislet dendritic cells bearing the β-cell-peptide-MHC complex. Here, we report that the entry of diabetogenic CD4 T cells very rapidly triggered inflammatory gene expression changes in islets and vessels by up-regulating chemokines and adhesion molecules. Vascular cell adhesion molecule-1 (VCAM-1) expression was notable in blood vessels, as was intercellular adhesion molecule-1 (ICAM-1). ICAM-1 was also found on β-cells. These expression changes induced the entry of nonspecific T cells that otherwise did not localize to the islets. In contrast to the entry of diabetogenic CD4 T cells, the entrance of nonspecific T cells required a chemokine response and VCAM-1 expression by the islets. IFN-γ was important for the early gene expression changes in the islets. By microarray analysis, we detected up-regulation of a group of IFN-inducible genes as early as 8 h post-T-cell transfer. These studies establish that entry of diabetogenic T cells induces a state of receptivity of islets to subsequent immunological insults.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Calderon
authors.forename: Javier A
authors.initials: JA
authors.lastname: Carrero
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Miller
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005784:Gene Amplification; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D000096743:Interferon gamma Receptor
chemical_list: D018398:Homeodomain Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D009113:Muramidase; D017471:Receptors, Interferon; D019010:Vascular Cell Adhesion Molecule-1; D000096743:Interferon gamma Receptor; C064658:RAG-1 protein; C421864:hen egg lysozyme