Antigen-specific immune modulation is emerging as an attractive therapeutic option to prevent atherosclerosis. We compared the efficacy of oral administration of peptides derived from apolipoprotein B (ApoB; 661–680) and heat shock protein 60 (HSP60; 153–163), in the prevention of atherosclerotic lesion formation hyperlipidemic low density lipoprotein receptordeficient (LDLr？/？), apolipoprotein B-100 only (apoB100/100) mice model. Oral administration of peptides induced tolerance as seen by an increase in regulatory T cells in the peripheral immune system. Tolerance to ApoB peptide reduced plaque development by 28.7% ( ) while HSP60 was effective in reducing lesion development by 26.8% in ApoB48/LDLr？/？ mice. While tolerance to HSP60 resulted in increase in anti-inflammatory cytokines (IL10 and TGF-β), ApoB tolerance was effective in reducing the lipid deposition in the lesion. Our results suggest that the two peptides have distinct mechanisms of controlling the development of atherosclerosis in mice. 1. Introduction Coronary artery disease remains the major cause of death and disability throughout the world despite the introduction of novel therapeutics [1]. Experimental observations in the past decade have proved that both innate and adaptive immune responses play an important role in the modulation of atherosclerosis. The complex role of the immune response in atherosclerosis is highlighted by the fact that they can contribute to both atheroprotective and proatherogenic effects [2–4]. The immune system generates regulatory T cells (Tregs), which actively suppress immune activation and maintain immune homeostasis [5, 6]. An imbalance between pathogenic T cells producing proatherogenic mediators and Treg cells with immunosuppressive properties is well established during the development of disease [7–9]. Thus antigen-specific immune modulation is emerging as an attractive therapeutic option to prevent inflammatory autoimmune diseases such as atherosclerosis [10–12]. The observation that immunization with modified low-density lipoproteins can reduce the atherosclerotic lesion in experimental models has opened the possibility that an atheroprotective vaccine can be developed [13–16]. Several antigens like the oxidized phospholipid molecules, modified apolipoprotein B-100 (ApoB) peptide, cholesteryl ester transfer protein, heat shock proteins, and vascular endothelial growth factor receptor have been used as a vaccine for the modification of immune response in atherosclerosis [4]. Immunotherapy is directed toward inducing tolerance to self-antigens
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