Physiological β cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model

S Turley, L Poirot, M Hattori, C Benoist… - The Journal of …, 2003 - rupress.org
S Turley, L Poirot, M Hattori, C Benoist, D Mathis
The Journal of experimental medicine, 2003rupress.org
The prelude to type-1 diabetes is leukocyte infiltration into the pancreatic islets, or insulitis.
This process begins in pancreatic lymph nodes when T lymphocytes reactive to islet β cells
encounter antigen-presenting cells (APCs) displaying peptides derived from β cell proteins.
We show here that a ripple of physiological β cell death, which occurs at 2 wk of age in all
mouse strains, precipitates the arrival of such APCs, and that the relevant APC is a dendritic
cell of CD11c+ CD11b+ CD8α− phenotype. These findings have significant implications …
The prelude to type-1 diabetes is leukocyte infiltration into the pancreatic islets, or insulitis. This process begins in pancreatic lymph nodes when T lymphocytes reactive to islet β cells encounter antigen-presenting cells (APCs) displaying peptides derived from β cell proteins. We show here that a ripple of physiological β cell death, which occurs at 2 wk of age in all mouse strains, precipitates the arrival of such APCs, and that the relevant APC is a dendritic cell of CD11c+CD11b+CD8α phenotype. These findings have significant implications concerning the nature of the diabetes-provoking deficits in NOD mice, the identity of the primordial diabetogenic antigens, and our understanding of the balance between immunity and tolerance in a pathological context.
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