| First Author | Hwang S | Year | 2012 |
| Journal | J Exp Med | Volume | 209 |
| Issue | 10 | Pages | 1781-95 |
| PubMed ID | 22945921 | Mgi Jnum | J:192915 |
| Mgi Id | MGI:5466807 | Doi | 10.1084/jem.20120058 |
| Citation | Hwang S, et al. (2012) Reduced TCR signaling potential impairs negative selection but does not result in autoimmune disease. J Exp Med 209(10):1781-95 |
| abstractText | Negative selection and regulatory T (T reg) cell development are two thymus-dependent processes necessary for the enforcement of self-tolerance, and both require high-affinity interactions between the T cell receptor (TCR) and self-ligands. However, it remains unclear if they are similarly impacted by alterations in TCR signaling potential. We generated a knock-in allele (6F) of the TCR zeta chain gene encoding a mutant protein lacking signaling capability whose expression is controlled by endogenous zeta regulatory sequences. Although negative selection was defective in 6F/6F mice, leading to the survival of autoreactive T cells, 6F/6F mice did not develop autoimmune disease. We found that 6F/6F mice generated increased numbers of thymus-derived T reg cells. We show that attenuation of TCR signaling potential selectively impacts downstream signaling responses and that this differential effect favors Foxp3 expression and T reg cell lineage commitment. These results identify a potential compensatory pathway for the enforcement of immune tolerance in response to defective negative selection caused by reduced TCR signaling capability. |
