Link H, Huang Y M, Masterman T, Xiao B G
Experimental Neurology and Neuroimmunology Units, Division of Neurology, Karolinska Institute, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
J Neuroimmunol. 2001 Mar 1;114(1-2):1-7. doi: 10.1016/s0165-5728(01)00247-8.
Autoimmune diseases such as multiple sclerosis (MS) are characterized by the loss of tolerance to self-determinants, activation of autoreactive lymphocytes and subsequent damage to single or multiple organs. The mechanisms by which autoimmune responses are triggered, and how activation of autoreactive lymphocytes is initiated and maintained, are not fully understood. Therapeutic approaches in autoimmune diseases have so far concentrated on antigens and T cells. Given the exceptional capacity of dendritic cells (DCs) to induce immunity in vivo, recent reports of the first successful clinical trials based on vaccination of tumor patients with autologous blood DCs pulsed in vitro with tumor antigen come as no surprise. The recent identification of tolerogenic subsets of DCs and their generation in culture may allow a novel approach to induce tolerance in autoimmune diseases. By selective in vitro manipulation of DCs and their subsequent reinfusion, DC-mediated tolerance has been achieved in animal models of human autoimmune diseases, including experimental autoimmune encephalomyelitis in Lewis rats and SJL/J mice and spontaneous diabetes in NOD mice. In vitro observations of human blood DCs are promising for DC-based treatment of MS and other diseases with an autoimmune component. Data from animal models and human materials suggest that DC-based immunotherapy could be beneficial at least as a complement to conventional therapy. Molecular-biological approaches to tolerogenic DCs could provide a rationale for designing immunotherapeutic strategies in autoimmune diseases.
自身免疫性疾病，如多发性硬化症（MS），其特征在于对自身抗原决定簇的耐受性丧失、自身反应性淋巴细胞的激活以及随后单个或多个器官的损伤。自身免疫反应被触发的机制，以及自身反应性淋巴细胞的激活是如何启动和维持的，目前尚未完全了解。迄今为止，自身免疫性疾病的治疗方法主要集中在抗原和T细胞上。鉴于树突状细胞（DCs）在体内诱导免疫的特殊能力，最近基于用肿瘤抗原体外脉冲处理的自体血液DCs对肿瘤患者进行疫苗接种的首次成功临床试验报告也就不足为奇了。最近对DCs的耐受性亚群及其在培养中的产生的鉴定，可能为在自身免疫性疾病中诱导耐受性提供一种新方法。通过对DCs进行选择性体外操作并随后回输，已在人类自身免疫性疾病的动物模型中实现了DC介导的耐受性，包括Lewis大鼠和SJL/J小鼠的实验性自身免疫性脑脊髓炎以及NOD小鼠的自发性糖尿病。对人类血液DCs的体外观察结果为基于DC的MS和其他具有自身免疫成分疾病的治疗带来了希望。来自动物模型和人类材料的数据表明，基于DC的免疫疗法至少作为传统疗法的补充可能是有益的。针对耐受性DCs的分子生物学方法可为设计自身免疫性疾病的免疫治疗策略提供理论依据。
