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T 细胞疫苗接种治疗自身免疫性疾病的机制与应用:全面综述

The mechanisms and applications of T cell vaccination for autoimmune diseases: a comprehensive review.

机构信息

Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Rd, Changsha, 410011, Hunan, People's Republic of China.

出版信息

Clin Rev Allergy Immunol. 2014 Oct;47(2):219-33. doi: 10.1007/s12016-014-8439-6.

Abstract

Autoimmune diseases (ADs) are a spectrum of diseases originating from loss of immunologic self-tolerance and T cell abnormal autoreactivity, causing organ damage and death. However, the pathogenic mechanism of ADs remains unclear. The current treatments of ADs include nonsteroidal anti-inflammatory drugs (NSAIDS), antimalarials, corticosteroids, immunosuppressive drugs, and biological therapies. With the need to prevent side effects resulting from current treatments and acquire better clinical remission, developing a novel pharmaceutical treatment is extremely urgent. The concept of T cell vaccination (TCV) has been raised as the finding that immunization with attenuated autoreactive T cells is capable of inducing T cell-dependent inhibition of autoimmune responses. TCV may act as an approach to control unwanted adaptive immune response through eliminating the autoreactive T cells. Over the past decades, the effect of TCV has been justified in several animal models of autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), murine autoimmune diabetes in nonobese diabetic (NOD) mice, collagen-induced arthritis (CIA), and so on. Meanwhile, clinical trials of TCV have confirmed the safety and efficacy in corresponding autoimmune diseases ranging from multiple sclerosis (MS) to systemic lupus erythematosus (SLE). This review aims to summarize the ongoing experimental and clinical trials and elucidate possible molecule mechanisms of TCV.

摘要

自身免疫性疾病(ADs)是一类起源于免疫自身耐受丧失和 T 细胞异常自身反应性的疾病,可导致器官损伤和死亡。然而,ADs 的发病机制仍不清楚。目前 ADs 的治疗方法包括非甾体抗炎药(NSAIDs)、抗疟药、皮质类固醇、免疫抑制剂和生物疗法。由于需要预防当前治疗方法引起的副作用并获得更好的临床缓解,开发新的药物治疗方法迫在眉睫。T 细胞疫苗接种(TCV)的概念已经提出,即免疫弱毒性自身反应性 T 细胞能够诱导 T 细胞依赖性抑制自身免疫反应。TCV 可能是一种通过消除自身反应性 T 细胞来控制不必要的适应性免疫反应的方法。在过去的几十年中,TCV 在几种自身免疫性疾病的动物模型中得到了证实,包括实验性自身免疫性脑脊髓炎(EAE)、非肥胖型糖尿病(NOD)小鼠的自身免疫性糖尿病、胶原诱导性关节炎(CIA)等。同时,TCV 的临床试验已经证实了其在从多发性硬化症(MS)到系统性红斑狼疮(SLE)等自身免疫性疾病中的安全性和有效性。本综述旨在总结 TCV 的正在进行的实验和临床试验,并阐明其可能的分子机制。

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