| First Author | Waldner H | Year | 2004 |
| Journal | J Clin Invest | Volume | 113 |
| Issue | 7 | Pages | 990-7 |
| PubMed ID | 15057305 | Mgi Jnum | J:89226 |
| Mgi Id | MGI:3039188 | Doi | 10.1172/JCI19388 |
| Citation | Waldner H, et al. (2004) Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease. J Clin Invest 113(7):990-7 |
| abstractText | We describe the generation of mice that express a transgenic T cell receptor (TCR) (5B6) specific for the encephalitogenic myelin proteolipid protein (PLP) peptide 139-151, on the experimental autoimmune encephalomyelitis-resistant (EAE-resistant) B10.S background. Despite harboring a high frequency of self-reactive T cells, 5B6 transgenic mice on the B10.S background rarely develop spontaneous EAE, which is in striking contrast to 5B6 transgenic mice on the EAE-susceptible SJL background. The relative resistance to spontaneous EAE in transgenic B10.S mice is not due to deletion or anergy of T cells, but appears to be controlled by APCs. Analysis of APCs revealed a lower activation state and a lower T cell-activating capacity for APCs from B10.S mice than for those from EAE-susceptible SJL mice. When APCs in 5B6 transgenic B10.S mice were activated, for example, via TLR9 or TLR4, T cell tolerance was broken, resulting in EAE. Our findings demonstrate that activation of APCs via innate immune receptors can break self tolerance and trigger the development of autoimmunity even in a genetically resistant strain. These findings suggest that the development of autoimmune diseases such as multiple sclerosis is determined at least partly by the endogenous activation state of APCs. |
