Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease - PubMed (original) (raw)

doi: 10.1038/nm1176. Epub 2005 Jan 16.

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

Affiliations

• PMID: 15654326
• DOI: 10.1038/nm1176

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

Karl S Lang et al. Nat Med. 2005 Feb.

Erratum in

• Nat Med. 2005 Nov;11(11):1256

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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Comment in

• A Toll-like trigger for autoimmune disease.
  Bach JF. Bach JF. Nat Med. 2005 Feb;11(2):120-1. doi: 10.1038/nm0205-120. Nat Med. 2005. PMID: 15692591 No abstract available.

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