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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Calderon, Boris Carrero, Javier A. Miller, Mark J. Unanue, Emil R. |
| Description | Author Affiliation: Calderon B ( Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.); |
| 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 ß-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 ß-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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CD4-Positive T-Lymphocytes Immunology Diabetes Mellitus, Type 1 Islets Of Langerhans Metabolism Adoptive Transfer Animals Blood Vessels Transplantation Dendritic Cells Genetics Flow Cytometry Gene Amplification Gene Expression Profiling Homeodomain Proteins Intercellular Adhesion Molecule-1 Interferon-gamma Blood Supply Mice Mice, Inbred NOD Mice, Knockout Mice, Transgenic Muramidase Oligonucleotide Array Sequence Analysis Receptors, Interferon Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Vascular Cell Adhesion Molecule-1 Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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