Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

13.10.2005


More than 150 years after the discovery of Hassall’s corpuscles in 1849, the function of these round blobs of cells in the human thymus gland has now been explained. The answer, in turn, ends an intense hunt for the origin of regulatory T cells that has been under way for years.



Reporting in the Aug. 25 issue of Nature, researchers at The University of Texas M. D. Anderson Cancer Center found that Hassall’s corpuscles produce chemical signals that instruct dendritic cells in the thymus to induce development of these regulatory T cells - the critically important immune system cells that patrol the body looking for "bad’ T cells that can produce autoimmune disease.

"These mysterious little structures in the thymus are responsible for producing the T cell policemen that our bodies depend so heavily on," says the study’s lead author, Yong-Jun Liu, M.D., Ph.D., professor and chair of the Department of Immunology. "It is a very smart system that evolved during evolution to efficiently keep the immune system in check."


The thymus functions like a school to educate immature immune system "T" (for thymus) cells. T cells are white blood cells that play vital roles in the immune system, including the identification of specific foreign "antigens" in the body (toxins, bacteria, viruses and other invading cells) and the activation and deactivation of other immune cells.

A chief function of the thymus is the selection of the T cell repertoire the immune system uses to combat infections - a process known as "clonal selection theory" that earned the researchers who discovered it a Nobel Prize in 1960. This involves the "positive selection" of T cells that are non self-reactive and the elimination, through "negative selection," of T cells that are self-reactive or autoreactive. If allowed outside of the thymus gland, these autoreactive T cells would produce a harmful immune response against the body’s own tissues, so the immune system flags "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 as was previously proposed by the clonal selection theory, but also through clonal conversion, as demonstrated in the current study.

The findings open new avenues in which to further explore the function of regulatory T cells in autoimmune disease and in cancer, the researchers say.

For example, mice experiments show that if regulatory T cells are destroyed, the animals will develop arthritis and other autoimmune diseases. So, if scientists can determine precisely how Hassall’s corpuscles and dendritic cells turn T cells into regulatory T cells, it may be possible to "convert" the errant T cells that promote an immune response in tissue into regulatory T cells, thus suppressing such disorders, Liu says.

Similarly, the discovery may help provide clues as to how cancer cells use regulatory T cells to work on their behalf, he says. One of the beneficial roles of regulatory T cells is to suppress the immune system (thus inactivating the damage caused by errant T cells), but "in cancer patients, regulatory T cells become troublemakers, because they suppress any natural reaction the immune system might have mounted to fight the cancer," Liu says.

"It may be that cancer is converting normal T cells into regulatory T cells to protect itself, and once we know the molecular language by which Hassall’s corpuscles and dendritic cells induce regulatory T cells, then we might understand how tumor cells also do this," he says.

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology

nachricht The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>