Fine tuning effector and regulatory T-cell dynamics: a novel tool for plaque regression?

Abstract

This editorial refers to ‘Regression of atherosclerosis with anti-CD3 antibody via augmenting a regulatory T-cell response in mice’ by T. Kita et al. , pp. 107–117, this issue. T cells are present during all stages of atherosclerosis development, and play an essential role in the initiation and progression of plaques. The majority of T lymphocytes in atherosclerotic lesions are CD4+ cells with a phenotype characteristic of the T-helper 1 (Th1) subset, producing high levels of IFN-γ.1,2 The generation of antigen-specific effector T lymphocytes during atherogenesis is likely to occur through self-antigens such as apolipoprotein (apo) B100 and oxidized low-density lipoprotein (LDL).1 Whereas most T effector cell responses have been suggested to aggravate atherosclerosis, regulatory T cells (Tregs) are increasingly recognized as potent atheroprotective players.3 Once activated, Tregs actively suppress responses of effector T cells by contact-dependent mechanisms or through the secretion of cytokines IL-10 and TGF-β. TGF-β plays a dual role in Tregs, as it regulates their differentiation and function but also is secreted as a potent effector cytokine. The functional role of Tregs in atherosclerosis models has been investigated either by direct adoptive transfer or by indirect measures such as vaccination.4,5 Another strategy is the administration of anti-CD3 antibodies (anti-CD3), either systemically or orally, which was shown to reduce atherosclerosis development at early and advanced stage.6,7 The anti-atherogenic effect of anti-CD3 involves TGF-β-dependent mechanisms via expansion and activation …