Author: ["Karl S Lang","Mike Recher","Tobias Junt","Alexander A Navarini","Nicola L Harris","Stefan Freigang","Bernhard Odermatt","Curdin Conrad","Lars M Ittner","Stefan Bauer","Sanjiv A Luther","Satoshi Uematsu","Shizuo Akira","Hans Hengartner","Rolf M Zinkernagel"]
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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-α production. These data identify the 'inflammatory status' of the target organ as a separate and limiting factor determining the development of autoimmune disease.Cite this article
Lang, K., Recher, M., Junt, T. et al. Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease. Nat Med 11, 138–145 (2005). https://doi.org/10.1038/nm1176 