| First Author | Pennington DJ | Year | 2006 |
| Journal | Nature | Volume | 444 |
| Issue | 7122 | Pages | 1073-7 |
| PubMed ID | 17190001 | Mgi Jnum | J:117487 |
| Mgi Id | MGI:3696604 | Doi | 10.1038/nature06051 |
| Citation | Pennington DJ, et al. (2006) Early events in the thymus affect the balance of effector and regulatory T cells. Nature 444(7122):1073-7 |
| abstractText | In cellular immunology the critical balance between effector and regulatory mechanisms is highlighted by serious immunopathologies attributable to mutations in Foxp3, a transcription factor required for a major subset of regulatory T (Tr) cells. Thus, many studies have focused on the developmental origin of Tr cells, with the prevailing view that they emerge in the thymus from late-stage T-cell progenitors whose T-cell receptors (TCRs) engage high affinity (agonist) ligands. This study questions the completeness of that interpretation. Here we show that without any obvious effect on TCR-mediated selection, the normal differentiation of mouse gammabeta T cells into potent cytolytic and interferon-gamma-secreting effector cells is switched towards an aggregate regulatory phenotype by limiting the capacity of CD4+CD8+ T-cell progenitors to influence in trans early gammabeta cell progenitors. Unexpectedly, we found that the propensity of early TCR-alphabeta+ progenitors to differentiate into Foxp3+ Tr cells is also regulated in trans by CD4+CD8+ T-cell progenitor cells, before agonist selection. |
