| First Author | Lang KS | Year | 2005 |
| Journal | Nat Med | Volume | 11 |
| Issue | 2 | Pages | 138-45 |
| PubMed ID | 15654326 | Mgi Jnum | J:96036 |
| Mgi Id | MGI:3528787 | Doi | 10.1038/nm1176 |
| Citation | Lang KS, et al. (2005) Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease. Nat Med 11(2):138-45 |
| abstractText | 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. |
