T cells are made in the thymus, a small organ situated under the breastbone near the heart, whose primary function is T-cell production. However, T cells ultimately come from hematopoietic (blood-producing) stem cells in the bone marrow, from which all blood-cell types begin. A progenitor cell leaves the bone marrow to seed the thymus, eventually giving rise to T cells. In the absence of instructions by the Notch protein, T-cell development does not occur, even in the presence of a normal thymus.
In this studypublished in the most recent issue of Nature Immunologythe investigators found that Notch, a protein that regulates diverse cell-fate decisions in multi-cellular organisms, is active in very early T-cell progenitors in the thymus of mice. Notch contributes to the subsequent differentiation of these early T-cell progenitors into T cells.
"Notch signaling instructs multi-potent progenitor cell types to enter the T-cell developmental pathway," says senior author Avinash Bhandoola, MD, PhD, Assistant Professor of Pathology and Laboratory Medicine. "However, we don't yet understand in which tissue these instructions are being delivered, and which cell type is the recipient."
Co-author Warren Pear, MD, PhD, Associate Professor of Pathology and Lab Medicine and member of Penn's Abramson Family Cancer Research Institute and Institute for Medicine and Engineering, was one of the original discoverers of the role of Notch in T-cell development. His lab developed tools to block Notch signaling, which were key to identifying its function in T-cell progenitors. Findings from this current study suggest that No
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
6-Jul-2005