| First Author | Martins GA | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 9 | Pages | 5981-5 |
| PubMed ID | 16237092 | Mgi Jnum | J:119336 |
| Mgi Id | MGI:3701877 | Doi | 10.4049/jimmunol.175.9.5981 |
| Citation | Martins GA, et al. (2005) Transcriptional activators of helper T cell fate are required for establishment but not maintenance of signature cytokine expression. J Immunol 175(9):5981-5 |
| abstractText | The stability of helper T cell fates is not well understood. Using conditional introduction of dominant-negative factors, we now show that T-bet and GATA-3 are far more critical in establishment than maintenance of IFN-gamma and IL-4 activity during Th1 and Th2 maturation, respectively. We also show that a genetic interaction between T-bet and its target Hlx seems to be required for Th1 maturation, but that Hlx may also be dispensable for maintenance of a transcriptionally permissive ifng gene. In parallel to progressive activator independence in the permissive lineage, the ifng gene becomes more recalcitrant to switching as the forbidden lineage matures. T-bet plus Hlx can disrupt ifng silencing when introduced into developing Th2 cells, but they fail to perturb ifng silencing in mature Th2 cells. In contrast, a hypermorphic allele of T-bet can reverse silencing of the ifng gene in mature Th2 cells. These results suggest that signature gene activity of helper T cells is initially plastic but later becomes epigenetically fixed and offer an initial strategy for inducing mature cells to switch their fate. |
