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They are young and need the job: A second chance for dangerous T-cells
Date:6/15/2009

The immune system's T-cells react to foreign protein fragments and therefore are crucial to combating viruses and bacteria. Errant cells that attack the body's own material are in most cases driven to cell death. Some of these autoreactive T-cells, however, undergo a kind of reeducation to become "regulatory T-cells" that keep other autoreactive T-cells under control. A group led by immunologist Professor Ludger Klein of LMU Munich has now shown that the developmental stage of an autoreactive T-cell is decisive to its ultimate destiny. Young autoreactive T-cells are very readily reeducated into regulatory T-cells. Under identical conditions, however, older T-cells become fully activated and can cause damage they are in a way resistant to reeducation. "We now intend to study at the molecular level what makes a T-cell accessible for reeducation," said Klein, "because then it may be possible to convert even normal adult T-cells, which can be obtained easily and in great numbers from blood. Possibly, they could then be used as regulatory T-cells in therapies for autoimmune diseases such as type-1 diabetes or multiple sclerosis: these are diseases that are triggered by uncontrolled autoreactive T-cells." (PNAS, 10 June 2009)

During their development in the thymus gland, a kind of 'T-cell school', every T-cell is fitted out with its own personal receptor. The diversity of these receptors allows the immune system to respond to nearly all pathogens. Since T-cell receptors are all randomly constructed, there is also a constant production of T-cells in the thymus that may recognize and attack the body's own structures. "Most of these dangerous autoreactive T-cells, though, are sorted out in a screening process before they leave the thymus," Klein reported. "This negative selection, that is the elimination of autoreactive T-cells that would otherwise attack their own organism, is an important requirement for immune tolerance."

But not all autoreactive
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Contact: Dr. Ludger Klein
ludger.klein@med.uni-muenchen.de
49-089-218-075-696
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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