ORIGINAL ARTICLE Iran J Allergy Asthma Immunol In press. The In vitro Effect of Oxidized LDL and PHA on Proliferation and Gene Expression of Regulatory T Cells of Patients with Atherosclerosis Azadeh Mottaghi 1 , Eisa Salehi 2 , Hashem Sezavar 3 , Seyed Ali Keshavarz 1 , Mohammad Reza Eshraghian 4 , Nima Rezaei 5,6 , Leili Rejali 7 , and Ali-Akbar Saboor-Yaraghi 1 1 Department of Nutrition and Biochemistry, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2 Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran 3 Department of Internal Medicine, Division of Cardiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 4 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 5 Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran 6 Department of Immunology, Molecular Immunology Research Center; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 7 Cellular and Molecular Biology, Medical Branch, Tehran Azad University, Tehran, Iran Received: 11 December 2011 ; Received in revised form: 9 January 2012 ; Accepted: 5 February 2012 ABSTRACT Atherosclerosis is a chronic inflammatory condition that affects the arterial wall. Oxidized low-density lipoprotein (ox-LDL) seems to have an important role in atherosclerotic plaque formation. This study was performed to investigate the effects of ox-LDL as well as PHA on proliferation and gene expression of T regulatory (Treg) cells in a group of patients with atherosclerosis. Peripheral blood mononuclear cells (PBMCs) of 31 atherosclerotic patients and 15 healthy controls were prepared. Proliferation of PBMCs was assessed by BrdU assay after stimulation of cells by PHA (10µg/mL) and ox-LDL (2µg/mL), while gene expression of Treg cells was assessed by real-time PCR. Both PHA and ox-LDL significantly induced proliferation of PBMCs of patients and controls (p<0.001). Stimulation of PBMCs with ox- LDL induced significantly higher proliferation in the controls than the patients (OD: 1.26±0.33 vs. 0.96±0.30, p=0.015). TGF-β expression level in the PBMCs of patient group was significantly lower than this value in healthy controls (p<0.001). Following simulation with PHA, TGF-β and Foxp3 gene expression levels in patients and controls were significantly decreased (p<0.001). Decreasing Foxp3 gene expression of PBMCs treated with ox-LDL was also significant in patients and controls. Decreased expression of TGF-β and Foxp3 genes after ox-LDL stimulation may be due to more sensitivity of Treg cells than effector T cells to ox-LDL. Presence of ox-LDL within atheroma could be associated with the diminished population of Treg in the atherosclerotic patients. Keywords: Atherosclerosis, Ox-LDL, Gene expression, T regulatory cells, Peripheral blood mononuclear cells Corresponding Author: Ali-Akbar Saboor-Yaraghi Department of Nutrition and Biochemistry, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Tel: (+98 21) , Fax: (+98 21) , E-mail: asaboor@sina.tums.ac.ir