Shimizu Kanako, Fujii Shin-ichiro
Research Unit for Therapeutic Model, The Institute of Physical and Chemical Research, RIKEN, Japan.
Front Biosci. 2008 May 1;13:6193-201. doi: 10.2741/3147.
Dendritic cells (DCs) work as a natural adjuvant to elicit T cell immunity. Though DCs have been widely used in immunotherapy, little is known about their number and function in patients with cancer or autoimmune disease. In recent studies, antigen has been targeted to DCs through DC-specific receptors, such as DEC205, the mannose receptor and dying cell receptors. However, antigen captured by DCs in the absence of danger signals induces tolerance. Therefore, the duration and/or magnitude of danger signals plays a crucial role in generating an immunogeneic response. Various danger signals, i.e., pathogen-associated molecular pattern (PAMP), damage-associated molecular pattern (DAMP) and the activation of innate lymphocytes, serve as maturation signals for DCs. An immunotherapeutic approach which delivers both maturation signals and antigen to DCs would link the innate and adaptive arms of the immune system for a more effective and global immune response. It is therefore crucial to determine optimal conditions for antigen delivery to DCs in an environment suited to maximally stimulate the immune system.
树突状细胞(DCs)作为天然佐剂发挥作用,以引发T细胞免疫。尽管DCs已广泛应用于免疫治疗,但对于癌症或自身免疫性疾病患者体内DCs的数量及功能,人们却知之甚少。在最近的研究中,抗原已通过DC特异性受体(如DEC205、甘露糖受体和死亡细胞受体)靶向至DCs。然而,在缺乏危险信号的情况下,DCs捕获的抗原会诱导免疫耐受。因此,危险信号的持续时间和/或强度在产生免疫原性反应中起着关键作用。各种危险信号,即病原体相关分子模式(PAMP)、损伤相关分子模式(DAMP)以及天然淋巴细胞的激活,均可作为DCs的成熟信号。一种将成熟信号和抗原均递送至DCs的免疫治疗方法,将把免疫系统的先天性和适应性分支联系起来,以产生更有效且全面的免疫反应。因此,确定在适合最大程度刺激免疫系统的环境中向DCs递送抗原的最佳条件至关重要。