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Wistar researchers: Direct proof of how T cells stay in 'standby' mode
Date:5/5/2011

t the Foxp1 protein is important for T cell development in the thymus. In order to understand how Foxp1 operates in mature T cells, the researchers used an inducible deletion model system where they could choose to delete the gene's activity after the cells have already matured.

In studying these Foxp1-less T cells, Hu and his colleagues discovered that naive T cells without Foxp1 become activated and proliferate in response to the protein IL-7, without antigen triggers. Hu and his colleagues discovered that Foxp1 represses the expression of the receptor for IL-7, and some other key signaling, in regulating T cell quiescence.

Foxp1, the researchers found, is similar to a related transcription factor, called Foxo1, a well-studied protein with numerous roles in both cancer and aging. In T cells, Foxo1 helps induce the creation of IL-7 receptors, which allows the T cell to receive the IL-7 signal. Foxp1, they found, directly competed with Foxo1's DNA binding spot, thereby limiting the number of IL-7 receptors each T cell has. Such inter-protein competition helps maintain a balanced state within the cell, Hu says.

Among their key findings, Hu believes, is that removing Foxp1 can cause T cells to proliferate without triggering the TCR. "Antigenic specificity is the key characteristic of T cells and our adaptive immunity," Hu. Said. "We never thought a naive T cell could be activated without stimulation through the T cell receptor."

"It came as such a surprise that the deletion of Foxp1, basically the removal of an essential negative regulation, could lead naive T cells to bypass overt antigen recognition and become activated with effector functions," Hu.

According to Hu, his laboratory, in collaboration with fellow laboratories at Wistar, are now investigating the possibility of knocking out Foxp1 to stimulate T cells in the tumor microenvironment.

"Many cancers cause local T cells to become effectively unrespo
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Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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