Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease

Détails

ID Serval
serval:BIB_A4C1D51E17FF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease
Périodique
Nature Medicine
Auteur(s)
Lang  K. S., Recher  M., Junt  T., Navarini  A. A., Harris  N. L., Freigang  S., Odermatt  B., Conrad  C., Ittner  L. M., Bauer  S., Luther  S. A., Uematsu  S., Akira  S., Hengartner  H., Zinkernagel  R. M.
ISSN
1078-8956 (Print)
Statut éditorial
Publié
Date de publication
02/2005
Volume
11
Numéro
2
Pages
138-45
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Résumé
Autoimmune diabetes mellitus in humans is characterized by immunological destruction of pancreatic beta islet cells. We investigated the circumstances under which CD8(+) T cells specific for pancreatic beta-islet antigens induce disease in mice expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) as a transgene under the control of the rat insulin promoter. In contrast to infection with LCMV, immunization with LCMV-GP derived peptide did not induce autoimmune diabetes despite large numbers of autoreactive cytotoxic T cells. Only subsequent treatment with Toll-like receptor ligands elicited overt autoimmune disease. This difference was critically regulated by the peripheral target organ itself, which upregulated class I major histocompatibility complex (MHC) in response to systemic Toll-like receptor-triggered interferon-alpha production. These data identify the 'inflammatory status' of the target organ as a separate and limiting factor determining the development of autoimmune disease.
Mots-clé
Animals Autoimmune Diseases/*immunology CD8-Positive T-Lymphocytes/*immunology Diabetes Mellitus, Type 1/*immunology/virology Genes, MHC Class I Humans Interferon-alpha/immunology Islets of Langerhans/cytology/metabolism/physiology Lymphocyte Activation Lymphocytic choriomeningitis virus/genetics/metabolism Membrane Glycoproteins/genetics/*immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Rats Receptors, Cell Surface/genetics/*immunology Toll-Like Receptors Transgenes Viral Proteins/genetics/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 16:04
Dernière modification de la notice
03/03/2018 20:14
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