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Researchers in Berlin, Germany have found that a specific type of immune cell, the regulatory T lymphocyte (Treg) plays an important role in hypertension-induced cardiac damage. The injected Treg that they harvested from donor mice into recipient mice were infused with angiotensin II, a blood pressure-raising peptide. The Tregs had no influence on the blood pressure response to angiotensin II. Nonetheless, cardiac enlargement, fibrosis, and inflammation was sharply reduced by Treg treatment. Dr. Heda Kvakan and Dr. Dominik N. Müller at the Experimental and Clinical Research Center at the Max Delbrück Center do not intend Treg as a therapy. (Circulation, June 9, 2009).
The researchers transferred Treg cells into mice. These cells normally keep the immune system in balance. If the number of Treg cells is reduced or their function impaired, the immune system gets out of balance and, rather than recognizing and destroying bacteria or viruses, the immune cells attack body tissue or organs instead. Autoimmune diseases, such as diabetes type I or Multiple sclerosis, result from the malfunctioning of the immune system.
Aside from its physiological role in maintaining blood pressure, it has long been known that the hormone angiotensin II plays a pivotal role in the onset of hypertension and in subsequnt hypertensive organ damage, e.g. cardiac hypertrophy.
Angiotensin II also has proinflammatory properties and actives the cells of the immune system. The activation of these cells also seems to have a major part in Angiotension II-induced target organ damage. The researchers wanted to know if the suppression of activated immune cells by Treg cells could reduce cardiac damage.
And indeed, hypertensive mice that had received Treg cells, exhibited less cardiac damage. "Hypertrophy and the thickening of the cardiac walls were reduced, also fibrosis and arrhythmia", Dr. Kvakan explains. The Treg cells had brought the immune cells under their control.
The work of Dr. Kvakan and Dr. Müller is the first study to examine the role of immunosuppressive Treg cells in the pathogenesis of hypertensive target organ damage. They conclude that hypertension-induced cardiac damage is partly due to immunological processes.
No Therapy
The two hypertension researchers make it clear that their experiments with Treg cells in mice are in no case suited for therapy in humans. One reason is that Treg cells are much more difficult to identify in humans than in mice. In addition, it is not known what side effects would occur in human patients following suppression of the immune system with Treg cells .
Nevertheless, Dr. Kvakan and Dr. Müller point out that hypertension can be treated well today.
It remains to be seen, if Treg cells will ever be used for short-time therapy. However, perhaps the body's own Treg could be recruited as a treatment.
*Regulatory T Cells Ameliorate Angiotensin II-Induced Cardiac Damage
Heda Kvakan, MD; Markus Kleinewietfeld, PhD; Fatimunnisa Qadri, PhD; Joon-Keun Park, PhD; Robert Fischer, MD; Ines Schwarz, MS; Hans-Peter Rahn, PhD; Ralph Plehm, MS; Maren Wellner, PhD; Saban Elitok, MD; Petra Gratze, MD; Ralf Dechend, MD; Friedrich C. Luft, MD; Dominik N. Muller, PhD
Received November 2, 2008; accepted April 7, 2009.
From the Franz Volhard Clinic, HELIOS Clinic Berlin-Buch, Berlin (H.K., S.E., P.G., R.D., F.C.L.); Max-Delbruck Center for Molecular Medicine
and Experimental and Clinical Research Center, Berlin (H.K., M.K., F.Q., R.F., I.S., H.-P.R., R.P., M.W., F.C.L., D.N.M.); and Medical School Hannover, Hannover (J.-K.P.), Germany.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.108.832782/DC1.
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
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e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/
http://www.mdc-berlin.de/en/news/2008/20081022-donor_cells_for_immune_therapy/in...
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