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In their search for the cellular and molecular causes of multiple sclerosis, an Italian-German research team has identified a subgroup of protective immune cells (suppressor cells) which are strikingly reduced in number in patients with this nervous system disorder. These suppressor cells are characterized by a specific surface marker, called CD39, and degrade ATP, an energy carrier released from damaged tissues. By this means, suppressor cells appear to be able to curb inflammation occurring in the central nervous system in the course of the disease. With CD39, Dr. Giovanna Borsellino (Laboratory for Neuroimmunology of the Fondazione Santa Lucia in Rome, Italy) in collaboration with Dr. Olaf Rötzschke and Dr. Kirsten Falk (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch, Germany) have for the first time identified a cellular marker whose disappearance can be directly correlated to the manifestation of multiple sclerosis.
As they report in the American journal Blood (Vol. 110, No. 4, pp. 1225-32, 2007), reduced numbers of CD39 suppressor cells may be indicative for the disease. At present, multiple sclerosis is diagnosed by testing for antibodies in the cerebrospinal fluid or by performing MRI scans of the brain. The future will show whether this new finding can also be useful for the development of a new therapy.
In multiple sclerosis, misdirected "auto-reactive" immune cells destroy the isolating myelin sheath surrounding the nerve fibers, disrupting the transmission of neuron signals. In healthy individuals, a special group of suppressor cells, also referred to as regulatory T cells, is one of the means how the body's defense-system keeps such amok-running immune cells in check.
Only recently, researchers in Heidelberg could show that the thymic production of regulatory T cells is impaired in patients with Multiple Sclerosis. In addition, research groups in Europe and the USA have revealed that genetic variations of two genes related to regulatory T cells can increase the risk of developing multiple sclerosis. The genes CD25 and CD127 encode the interleukin receptors 7 and 2, which regulate the activation of immune cells.
*Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression
Giovanna Borsellino1, Markus Kleinewietfeld2, Diletta Di Mitri1, Alexander Sternjak2, Adamo Diamantini1, Raffaella Giometto1, Sabine Höpner2, Diego Centonze3, Giorgio Bernardi3, Maria Luisa Dell'Acqua4, Paolo Maria Rossini4, Luca Battistini1, Olaf Rötzschke2 and Kirsten Falk2
Present address: 1Laboratory of Neuroimmunology, Fondazione Santa Lucia, Via del Fosso di Fiorano 65, 00143 Rome, Italy; 2Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, D-13125 Berlin, Germany; 3Neurology Unit, Universita' di Roma Tor Vergata, Via Montpellier 1 Rome Italy, 4Neurology Unit, University of Rome Campus Biomedico, Rome, Italy
Corresponding authors: Kirsten Falk*, Olaf Rötzschke
Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, D-13125 Berlin, Germany; Tel: +49 30 9406, 3664, FAX: +49 30 9406 2394 ; falk@mdc-berlin.de, roetzsch@mdc-berlin.de
Blood First Edition Paper, prepublished online April 20, 2007; DOI 10.1182/blood-2006-12-064527
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
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http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm
http://bloodjournal.hematologylibrary.org/
<http://www.nature.com/ni/journal/v8/n6/full/ni0607-561.html ("Suppression strategy")>
http://www.jimmunol.org/content/vol179/issue2/
http://www.nature.com/ng/journal/vaop/ncurrent/pdf/ng2103.pdf
http://www.nature.com/ng/journal/vaop/ncurrent/pdf/ng2106.pdf
http://content.nejm.org/cgi/content/full/NEJMe078147?resourcetype=HWCIT
http://content.nejm.org/cgi/content/full/328/16/1173
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