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Old mystery solved, revealing origin of regulatory T cells that 'police' and protect the body

dendritic" cells within the thymus to eliminate these bad cells. T cells that pass both levels of selection are then released into the bloodstream to perform vital immune functions.

"It was believed that the only way to induce what is known as central tolerance was by deleting harmful T cells during development," says Liu.

But scientists now know that not all the "bad" T cells are destroyed through negative selection. Some autoreactive T cells escape the thymic censorship process and are released into the circulation. For that reason, researchers searched for additional mechanisms that exist in the blood and lymph system outside of the thymus to take care of these bad actors - which led to the discovery of regulatory T cells. These special T cells act like policemen to scour out dangerous T cells and suppress activation of the immune system, and thus maintain tolerance to self.

A major question in immunology was how regulatory T cells are developed in the thymus.

In 2002, in Nature Immunology, Liu and his research team revealed the existence of the chemical signal TSLP (thymic stromal lymphopoietin) that activates dendritic cells in the thymus. In 2004, they reported, also in Nature Immunology, that epithelial cells within Hassall's corpuscles express TSLP.

In this study, using human thymus tissue taken during cardiac surgery in children - tissue that otherwise would have been discarded " the researchers isolated different components of thymic cells, and reconstituted them in test tubes. They then conducted numerous experiments over several years, looking at different stages of T cell development and activation of dendritic cells.

They found that Hassall's corpuscles produce chemical signals that direct a specialized group of dendritic cells to turn some of the bad T cells into "good cop" regulatory T cells.

This means that the thymus is providing central tolerance not only through clonal deletion
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Contact: Nancy Jensen
nwjensen@mdanderson.org
713-792-0655
University of Texas M. D. Anderson Cancer Center
11-Oct-2005


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