Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47

The E2A proteins, E12 and E47, are required for progression through multipl e developmental pathways, including early B and T lymphopoiesis. Here, we p rovide in vitro and in vivo evidence demonstrating that E47 activity regula tes double-positive thymocyte maturation. In the absence of E47 activity po sitive selection of both major histocompatibility complex (MHC) class I- an d class II-restricted T cell receptors (TCRs) is perturbed. Additionally, d evelopment of CD8 Lineage T cells in an MHC class I-restricted TCR transgen ic background is sensitive to the dosage of E47. Mice deficient for E47 dis play an increase in production of mature CD4 and CD8 lineage T cells. Furth ermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id 3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection.