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- Title
Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease.
- Authors
Lang, Karl S; Recher, Mike; Junt, Tobias; Navarini, Alexander A; Harris, Nicola L; Freigang, Stefan; Odermatt, Bernhard; Conrad, Curdin; Ittner, Lars M; Bauer, Stefan; Luther, Sanjiv A; Uematsu, Satoshi; Akira, Shizuo; Hengartner, Hans; Zinkernagel, Rolf M
- 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.
- Publication
Nature medicine, 2005, Vol 11, Issue 2, p138
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm1176