A mimic of viral double-stranded RNA triggers fulminant type 1 diabetes-like syndrome in regulatory T cell-deficient autoimmune diabetic mouse.
J Immunol
; 187(10): 4947-53, 2011 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-21967896
ABSTRACT
Human fulminant type 1 diabetes (FT1D) is an extremely aggressive disease. The delay of proper diagnosis results in high mortality. However, the pathophysiology of this disease remains unclear. We took advantage of CD28-deficient NOD (CD28(-/-) NOD) mice, which have limited numbers of regulatory T cells and develop aggressive autoimmune diabetes, to create a FT1D model that mimicked the disease in humans. Young CD28(-/-) NOD mice were injected with polyinosinic-polycytidylic acid to activate innate immunity in an effort to induce diabetes onset. In this model, innate immune cell activation precedes the onset of diabetes similar to â¼70% of FT1D patients. Eighty-three percent of CD28(-/-) NOD mice developed diabetes within 1-6 d after injection of polyinosinic-polycytidylic acid. Moreover, T cells infiltrated the pancreatic exocrine tissue and destroyed α cells, an observation characteristic of human FT1D. We conclude that an FT1D-like phenotype can be induced in the background of autoimmune diabetes by a mimic of viral dsRNA, and this model is useful for understanding human FT1D.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Bicatenario
/
ARN Viral
/
Linfocitos T Reguladores
/
Imitación Molecular
/
Diabetes Mellitus Tipo 1
/
Linfopenia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón