| First Author | Schietinger A | Year | 2012 |
| Journal | Science | Volume | 335 |
| Issue | 6069 | Pages | 723-7 |
| PubMed ID | 22267581 | Mgi Jnum | J:181282 |
| Mgi Id | MGI:5310692 | Doi | 10.1126/science.1214277 |
| Citation | Schietinger A, et al. (2012) Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state. Science 335(6069):723-7 |
| abstractText | Tolerant self-antigen-specific CD8 T cells fail to proliferate in response to antigen, thereby preventing autoimmune disease. By using an in vivo mouse model, we show that tolerant T cells proliferate and become functional under lymphopenic conditions, even in a tolerogenic environment. However, T cell rescue is only transient, with tolerance reimposed upon lymphorepletion even in the absence of tolerogen (self-antigen), challenging the prevailing paradigm that continuous antigen exposure is critical to maintain tolerance. Genome-wide messenger RNA and microRNA profiling revealed that tolerant T cells have a tolerance-specific gene profile that can be temporarily overridden under lymphopenic conditions but is inevitably reimposed, which suggests epigenetic regulation. These insights into the regulatory mechanisms that maintain or break self-tolerance may lead to new strategies for the treatment of cancer and autoimmunity. |
