European Heart Journal Advance Access originally published online on September 5, 2006
European Heart Journal 2006 27(21):2530-2537; doi:10.1093/eurheartj/ehl222
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Altered status of CD4+CD25+ regulatory T cells in patients with acute coronary syndromes
Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv 64239, Israel
Received 9 March 2006; revised 16 July 2006; accepted 17 August 2006; online publish-ahead-of-print 5 September 2006.
* Corresponding author. Tel: +972 53 550616; Fax: +972 3 5469832.E-mail address: jacobg{at}post.tau.ac.il
See page 2485 for the editorial comment on this article (doi:10.1093/eurheartj/ehl284)
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.
Key Words: Atherosclerosis T cells Immune response Acute coronary syndrome Foxp3
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