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

tal protective functions. Certain lung infections easily cleared from normal laboratory mice are a death sentence for those lacking gamma-delta T cells.

Despite their clear importance in resisting disease, the processes controlling the generation of gamma-delta T cells have remained mysterious until recently. As Robert Frost put it, Wiest pointed out:
"Two roads diverged in a wood, and I--
I took the one less traveled by,
And that has made all the difference."

"Gamma-delta T cells represent the road less traveled," Wiest said. "However, the role of the TCR in determining lineage is controversial, particularly whether different forms of TCR predetermine a cell's fate and whether or not their signals control the choice."

In the new study, Wiest and his colleagues use several models to manipulate the signaling strength of the gamma-delta TCR. A strong signal, produced in the presence of a specific binding substance, or ligand, directs immature T cells almost exclusively to the gamma-delta lineage. However, weakening the signal promotes alpha-beta lineage development.

"The signal strength determines the level of expression of early growth response (Egr) proteins, with cells choosing the gamma-delta lineage expressing far greater quantities of Egr proteins than those adopting the alpha-beta lineage," explained Wiest. "Egr proteins regulate which cellular genes are turned on or off so we think that high-level expression of Egr proteins instructs cells to express the set of cellular genes necessary to become a gamma-delta T cell."

Understanding the development of critical components of the immune system can lead to scientific and medical advances in stimulating desirable immune responses and halting unwanted ones.

"Although their precise function is still unclear, delta-gamma T cells seem to form the first line of response against external disease-causing agents, including bacterial infections, tissue damage
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Source:Fox Chase Cancer Center


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