Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model.
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 beta cells encounter antigen-presenting cells (APCs) displaying peptides derived from beta cell proteins. We show here that a ripple of physiological beta 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+CD8alpha- 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.
Turley
Shannon
S
Section of Immunology and Immunogenetics, Joslin Diabetes Center and Dept. of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Pl., Boston, MA 02215, USA.
Poirot
Laurent
L
Hattori
Masakazu
M
Benoist
Christophe
C
Mathis
Diane
D
D000818:Animals; D001402:B-Lymphocytes; D016923:Cell Death / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D007515:Islets of Langerhans / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*