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Fox Chase study shows that weakened T-cell receptor signals change T-cell lineage

The immune system is a marvel of versatility, creating a variety of cells that develop in different ways to protect the body. To carry out these tasks, immune cells follow a career path that forks at various points in their development. In a report in the May 2005 issue of Immunity, Fox Chase Cancer Center scientists led by immunologists David L. Wiest, Ph.D. and Dietmar J. Kappes, Ph.D., show that cell-receptor signaling strength influences which course certain immature immune cells will take, suggesting a flexible new model for commitment to one lineage or another.

The first, most basic career choice made by precursors of the adaptive arm of the immune system is whether to adopt the B-cell or T-cell fate. Both originate from stem cells in the bone marrow, but B cells mature there while T cells migrate to the thymus gland, which governs their development.

"The recognition and destruction of invading pathogens by T lymphocytes is essential to the ability of humans to resist disease," said Wiest. "T cells recognize these invaders by means of a surface structure called the T-cell antigen receptor complex, or TCR."

Two distinct lineages of T cells utilize distinct types of TCR complexes. One lineage employs pairs of TCR proteins termed alpha-beta while the other uses the TCR gamma-delta pair of proteins. The alpha-beta and gamma-delta pairs of proteins represent the "eyes" of the TCR complex and enable these distinct types of T cells make unique contributions to our ability to resist disease.

The more numerous T cells of the alpha-beta lineage provide protection against infectious diseases either by helping B cells generate antibodies against external agents (helper T cells) or by directly attacking and destroying cells infected by foreign invaders (killer T cells). Gamma-delta T cells migrate from the thymus to epithelial tissues such as skin and the linings of the lung. While their precise role remains poorly understood, they p
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Contact: Karen Carter Mallet
Karen.Mallet@fccc.edu
215-728-2700
Fox Chase Cancer Center
17-May-2005


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