European Heart Journal Advance Access published online on September 5, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl222
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1 Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv 64239, Israel
* To whom correspondence should be addressed. Aims Considerable evidence supports the role of innate and adaptive immunity in the progression and destabilization of the atheromatous plaque. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are a subpopulation of lymphocytes that are capable of suppressing the progression of experimental autoimmune disorders. We have hypothesized that peripheral numbers and function of Tregs would be deranged in patients with acute coronary syndromes (ACS). Methods and results Peripheral numbers of Tregs were evaluated by FACS employing labelled antibodies to CD4 and CD25. Functional suppressive properties of Tregs were assayed by establishing a triple-cell culture in which purified Tregs were incubated with irradiated antigen-presenting cells and anti-CD3-activated responder T cells. Proliferation in the presence or absence of oxidized LDL (oxLDL) was evaluated by thymidine incorporation. mRNA and protein content of foxp3, a master transcriptional regulator of Tregs, were determined for all subjects. Patients with ACS exhibited significantly reduced numbers of peripheral Tregs as compared with patients with stable angina and normal coronary artery subjects. Moreover, oxLDL induced a more profound reduction in Treg numbers in patients with ACS. Tregs in ACS patients were significantly compromised as their ability to suppress responder CD4+CD25- T-cell proliferation was attenuated. mRNA and protein content of foxp3 were significantly reduced in purified Tregs obtained from patients with ACS. Conclusion In patients with ACS, naturally occurring CD4+CD25+ Treg numbers are reduced and their functional properties compromised. These findings may aid in understanding the mechanisms leading to culprit plaque associated T-cell activation in patients with ACS.
Received March 9, 2006
Revised July 16, 2006
Accepted August 17, 2006
Clinical research
Altered status of CD4+CD25+ regulatory T cells in patients with acute coronary syndromes
Adi Mor 1, Galia Luboshits 1, David Planer 1, Gad Keren 1, and Jacob George 1 *
Jacob George, E-mail: jacobg{at}post.tau.ac.it
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