Experimental Cardiovascular Research Unit, Clinical Sciences, Clinical Research Center, Lund University, Lund, Sweden.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
J Intern Med. 2015 Nov;278(5):507-19. doi: 10.1111/joim.12353.
Emerging knowledge of the role of atheroprotective immune responses in modulating inflammation and tissue repair in atherosclerotic lesions has provided promising opportunities to develop novel therapies directly targeting the disease process in the artery wall. Regulatory T (Treg) cells have a protective role through release of anti-inflammatory cytokines and suppression of autoreactive effector T cells. Studies in experimental animals have shown that blocking the generation or action of Treg cells is associated with more aggressive development of atherosclerosis. Conversely, cell transfer and other approaches to expand Treg cell populations in vivo result in reduced atherosclerosis. There have been relatively few clinical studies of Treg cells and cardiovascular disease, but the available evidence also supports a protective function. These observations have raised hope that it may be possible to develop therapies that act by enforcing the suppressive activities of Treg cells in atherosclerotic lesions. One approach to achieve this goal has been through development of vaccines that stimulate immunological tolerance for plaque antigens. Several pilot vaccines based on LDL-derived antigens have demonstrated promising results in preclinical testing. If such therapies can be shown to be effective also in clinical trials, this could have an important impact on cardiovascular prevention and treatment. Here, we review the current knowledge of the mode of action of atheroprotective immunity and of the ways to stimulate such pathways in experimental settings. The challenges in translating this knowledge into the clinical setting are also discussed within the perspective of the experience of introducing immune-based therapies for other chronic noninfectious diseases.
关于动脉粥样硬化病变中保护性免疫反应在调节炎症和组织修复方面的作用的新知识，为开发直接针对动脉壁疾病过程的新型疗法提供了有希望的机会。调节性 T（Treg）细胞通过释放抗炎细胞因子和抑制自身反应性效应 T 细胞发挥保护作用。实验动物研究表明，阻断 Treg 细胞的生成或作用与动脉粥样硬化的更具侵袭性发展有关。相反，细胞转移和其他在体内扩增 Treg 细胞群体的方法可导致动脉粥样硬化减少。关于 Treg 细胞和心血管疾病的临床研究相对较少，但现有证据也支持其保护功能。这些观察结果带来了希望，即有可能开发通过在动脉粥样硬化病变中强化 Treg 细胞的抑制活性来发挥作用的疗法。实现这一目标的一种方法是开发针对斑块抗原的免疫耐受疫苗。几种基于 LDL 衍生抗原的试验性疫苗在临床前测试中显示出有希望的结果。如果此类疗法在临床试验中也被证明有效，这将对心血管预防和治疗产生重要影响。在这里，我们综述了保护性免疫作用的作用模式以及在实验环境中刺激这些途径的方法的现有知识。还从引入其他慢性非传染性疾病的免疫疗法的经验的角度讨论了将这些知识转化为临床环境的挑战。
