Bhargava P, Calabresi P A
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clin Exp Immunol. 2015 Jun;180(3):353-60. doi: 10.1111/cei.12602. Epub 2015 Apr 23.
Autoimmune diseases are a major cause of morbidity, and their incidence and prevalence continue to rise. Treatments for these diseases are non-specific and result in significant adverse effects. Targeted therapies may help in improving the risk : benefit ratio associated with treatment. Immunological memory is an important feature of the vertebrate immune system that results in the production of cells that are long-lived and able to respond to antigens in a more robust manner. In the setting of autoimmunity this characteristic becomes detrimental due to the ongoing response to a self-antigen(s). These memory cells have been shown to play key roles in various autoimmune diseases such as type 1 diabetes, multiple sclerosis and psoriasis. Memory T cells and B cells can be identified based on various molecules expressed on their surface. Memory T cells can be divided into three main categories - central memory, effector memory and resident memory cells. These subsets have different proliferative potential and cytokine-producing abilities. Utilizing differentially expressed surface molecules or downstream signalling pathway proteins in these cells it is now possible to target memory cells while sparing naive cells. We will discuss the various available options for such a strategy and several potential strategies that may yield successful therapies in the future.
自身免疫性疾病是发病的主要原因,其发病率和患病率持续上升。这些疾病的治疗方法缺乏特异性,且会产生显著的副作用。靶向治疗可能有助于改善治疗的风险效益比。免疫记忆是脊椎动物免疫系统的一个重要特征,它会产生长寿的细胞,并能以更强大的方式对抗原作出反应。在自身免疫的情况下,由于对自身抗原的持续反应,这一特性变得有害。这些记忆细胞已被证明在各种自身免疫性疾病中起关键作用,如1型糖尿病、多发性硬化症和银屑病。记忆T细胞和B细胞可以根据其表面表达的各种分子来识别。记忆T细胞可分为三大类——中枢记忆细胞、效应记忆细胞和驻留记忆细胞。这些亚群具有不同的增殖潜力和细胞因子产生能力。利用这些细胞中差异表达的表面分子或下游信号通路蛋白,现在有可能靶向记忆细胞,同时保留幼稚细胞。我们将讨论这种策略的各种可用选项,以及未来可能产生成功治疗方法的几种潜在策略。