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Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular response.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 1/25/2011, Vol. 108 Issue 4, p1567-1572. 6p. 1 Color Photograph, 5 Graphs. - Publication Year :
- 2011
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *T cells
*DIABETES
*LANGERHANS cells
*DENDRITIC cells
*GENE expression
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 108
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 58769969
- Full Text :
- https://doi.org/10.1073/pnas.1018975108