References
Query Results -- Details
MGI Accession ID: MGI:3528787
J Number: J:96036
Other Accession IDs:
Title: Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease.
Authors: Lang KS; Recher M; Junt T; Navarini AA; Harris NL; Freigang S; Odermatt B; Conrad C; Ittner LM; Bauer S; Luther SA; Uematsu S; Akira S; Hengartner H; Zinkernagel RM
Journal: Nat Med
Volume: 11
Issue: 2
Date: 2005 Feb
Year: 2005
Pages: 138-45
Review Status: Peer Reviewed
Abstract:
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.
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