The opposite-direction modulation of CD4+CD25+ Tregs and T helper 1 cells in acute coronary syndromes Shu-fang Han a, ⁎ ,1 , Peng Liu b,1 , Wei Zhang a,1 , Lun Bu a,1 , Min Shen a,1 , Hu Li a , Yan-hong Fan a , Kang Cheng a , He-xiang Cheng a , Cheng-xiang Li a , Guo-liang Jia a a Department of Cardiology, Xijing hospital, Fourth Military Medical University, Xi’an, PR China b Department of Oral Histology and Pathology, College of Stomatology, Fourth Military Medical University, Xi’an, PR China Received 6 December 2006; accepted with revision 28 March 2007 Available online 23 May 2007 Abstract Different subsets of T lymphocytes have different functions in atherosclerosis advancement. T helper 1 cells and T regulatory 1 cells have been demonstrated to play opposite roles in rupture of atherosclerotic lesion. However, the role of novel subset of Tregulatory cells, known as CD4+CD25+Foxp3+ T cells, remains largely unknown in coronary artery disease (CAD). In this study, we investigated the peripheral CD4+CD25+Foxp3+ T cells of patients with CAD and controls. The patients submitted were divided into three groups: stable angina pectoris (SA) group, unstable angina pectoris (UA) group and acute myocardial infarction (AMI) group. We analyzed the frequencies of peripheral CD4+CD25+Foxp3+ T cells and T helper 1/T helper 2 cells, expression of Foxp3 in CD4+CD25+ T subsets and cytokines pattern in patients and controls. We found that the reduction of CD4+CD25+Foxp3+ T lymphocytes was consistent with the expansion of Th1 cells in patients with unstable CAD. The reversed development between CD4+CD25+ Tregs and Th1 cells might contribute to plaque destabilization. © 2007 Elsevier Inc. All rights reserved. KEYWORDS Atherosclerosis Immunity Lymphocytes Destabilization Introduction Atherosclerosis is a chronic inflammatory disease of the arterial wall [1,2]. Inflammation can induce a cascade of events that amplify immune cell infiltration, platelet activation and adhesion, plaque rupture and intermittent arterial occlusion, leading to acute coronary syndrome (ACS). The activation of inflammatory pathways in ACS is not confined to the coronary lesions but includes stimulation of circulation lymphocytes. Solid evidence showed that circulating CD4+ T lymphocytes preferentially differentiated into Th1 cells in the transition of the plaques from a ‘silent’ to a ‘vulnerable’ phenotype [3–5]. Strongly Th1-polarized immune response instigates the production of many inflam- matory cytokines, such as IFN-γ, IL-2, IL-12 and TNF-α and accelerates endothelium or smooth muscle cells injury [6,7]. The dominance of proinflammatory Th1 response over Th2 ⁎ Corresponding author. Fax: +86 29 83251287. E-mail address: tangchao@fmmu.edu.cn (S. Han). 1 The authors contributed equally to this work. 1521-6616/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.clim.2007.03.546 available at www.sciencedirect.com www.elsevier.com/locate/yclim Clinical Immunology (2007) 124, 90–97