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Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immuno-inflammatory mechanisms are involved. Inflammation is central at all stages of atherosclerosis. It is implicated in the formation of early fatty streaks, when the endothelium is activated and expresses chemokines and adhesion molecules leading to monocyte/lymphocyte recruitment and infiltration into the subendothelium. It also acts at the onset of adverse clinical vascular events, when activated cells within the plaque secrete matrix proteases that degrade extracellular matrix proteins and fragilize the fibrous cap, leading to rupture and thrombus formation. Cells involved in the atherosclerotic process secrete and are activated by pro-inflammatory cytokines. Recent advances in our understanding of the mechanisms of atherosclerosis provided evidence that the immuno-inflammatory response in atherosclerosis is modulated by regulatory pathways involving the two anti-inflammatory cytokines IL-10 and TGF-β, which play a critical role in counter-balancing the effects of pro-inflammatory cytokines. Interestingly, IL-10 and TGF-β are also the two cytokines that mediate the immune regulatory functions of a sub-population of T cells, named regulatory T (Treg) cells. We recently demonstrated that natural CD4+CD25+ Treg cells play an important role in the control of atherosclerosis in apoE-/- mice. It is therefore believed that atherosclerosis may result from an imbalance between pathogenic T cells, either Th1 or Th2, producing pro-atherogenic mediators, and Treg cells with immunosuppressive properties, and that promotion, expansion or exogenous administration of Treg cells might limit disease development and progression.
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J. Vasc. Biol. 42, Sup:2 (2005) p5