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

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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Nat Med, 11, 2, 138-45
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 Research Support, Non-U.S. Gov't United States Nature medicine Nat Med. 2005 Feb;11(2):138-45. Epub 2005 Jan 16.

 Record created 2010-01-06, last modified 2018-03-17

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