| First Author | Chang X | Year | 2006 |
| Journal | Clin Immunol | Volume | 121 |
| Issue | 3 | Pages | 274-85 |
| PubMed ID | 16945588 | Mgi Jnum | J:115967 |
| Mgi Id | MGI:3692513 | Doi | 10.1016/j.clim.2006.07.004 |
| Citation | Chang X, et al. (2006) Foxp3 controls autoreactive T cell activation through transcriptional regulation of early growth response genes and E3 ubiquitin ligase genes, independently of thymic selection. Clin Immunol 121(3):274-85 |
| abstractText | To elucidate the mechanisms of autoreactive T cell activation and expansion, we used endogenous viral superantigens (VSAg)-reactive T cells as a model of self-antigens in two strains of Foxp3-mutant mice. These two strains, together with wild-type mice, provided us with an advantage to simultaneously study the positively and negatively selected as well as rescued autoreactive T cells. We show here that while both VSAg-reactive and non-VSAg-reactive T cells are equally activated in Foxp3-mutant mice, only the VSAg-reactive T cells are preferentially expanded independently of their selected states in the thymus. The T cell activation appears to be controlled by Foxp3 through transcriptional regulation of early growth response (Egr) genes Egr-2 and Egr-3, and E3 ubiquitin (Ub) ligase genes Cblb, Itch and GRAIL, subsequently affecting degradation of two key signaling proteins, PLCgamma1 and PKC-theta. Physiologically, the positively, but not negatively selected VSAg-reactive T cells are spontaneously activated without significant expansion. The results suggest that autoreactive T cell activation is controlled by Foxp3 through transcriptional regulation of early growth response genes and E3 ubiquitin ligase genes, independently of thymic selection. |
