Protective Immunity in Atherosclerosis

Abstract: The immune system is a promising target for novel therapies that are aiming at reducing cardiovascular diseases. Autoimmune responses against modified low density lipoprotein (LDL) are believed to promote development of atherosclerosis. Proinflammatory immune responses can be counterbalanced by immunosuppressive regulatory T cells (Tregs). Immunizations of hypercholesterolemic mice with oxidized LDL or peptides derived from the protein part of LDL, apoB-100, inhibit the development of atherosclerosis. The protective immunity induced by the apoB-100 peptide vaccine aBp210 is associated with an activation of Tregs indicating that specific activation of Tregs could be a promising target in immune modulating therapies. Activation of the inhibitory Fcgamma receptor IIB (FcgammaRIIB) is an additional potential target for immune modulating therapy as hypercholesterolemic mice deficient in FcgammaRIIB have a more aggressive disease development. Antigen presentation is a fundamental step in T cell activation. By investigating the role of antigen presentation in atherosclerosis development new targets for intervention could be provided. Antigen presentation on major histocompatibility complex (MHC) class II is critical in activation of CD4+ T cells whereas CD1d antigen presentation is required for activation of NKT cells. The role of MHC class II antigen presentation in atherosclerosis is complex and was unexpectedly found to be associated with reduced atherosclerosis development, whereas, neointima formation in response to vascular injury was accelerated by CD1d lipid antigen presentation. NKT cells and CD1d could therefore be an additional potential target in immune modulating therapies. Except for novel therapies, new biomarkers to better predict development of acute cardiovascular events are also needed in order to reduce the disease. Low levels of circulating Tregs may be a future predictor for myocardial infarction and stroke.