PHILADELPHIA In the latest issue of Nature, researchers at the Perelman School of Medicine at the University of Pennsylvania clarify the role of two proteins key to T-cell development. They found that one well-known protein called Notch passes off much of its role during T-cell maturation to another protein called TCF-1. T cells are required for many aspects of immunity, and understanding how these proteins influence the production of infection-fighting cells could improve treatments for immune-suppressed patients.
The research group, led by senior author Avinash Bhandoola, MBBS, PhD, associate professor of Pathology and Laboratory Medicine, found an important role in early T-cell development for T-cell factor 1 (TCF-1), which is turned on by Notch signals.
"Notch triggers the process of T-cell development, and turns on expression of TCF-1, but Notch itself doesn't stick around; it's more of a kiss-and-run molecule," says Bhandoola. In contrast, once induced by Notch, TCF-1 is faithfully expressed throughout T-cell maturation.
T cells are made in the thymus, a small organ situated under the breastbone near the heart. However, T cells, like all blood-cell types, originate from blood-producing stem cells in the bone marrow. Immature T-cell progenitors leave the bone marrow, settle within the thymus, and eventually give rise to T cells.
Notch regulates cell-fate decisions in many cell types in addition to immune cells. Past work at Penn helped demonstrate that Notch is active in early T-cell progenitors in the thymus of mice, and drives the differentiation of these progenitors down the T cell pathway.
Co-first authors, Anthony Wei-Shin Chi, MD, PhD, and Brittany Nicole Weber, BS, were graduate students together in the Bhandoola lab. They used retroviruses to express TCF-1 in immature blood progenitor cells. "If you expose progenitor cells to Notch signals in culture, we know that t
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine