Targeting dendritic cells for priming cellular immune responses
Targeting dendritic cells for priming cellular immune responses
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DOI：
10.1002/jmr.650
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发表时间：
2003-09-01
影响因子：
2.7
通讯作者：
Rajnavölgyi, É
中科院分区：
文献类型：
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作者：
Gogolák, P;Réthi, B;Rajnavölgyi, É
针对所有种类的病原体以及针对肿瘤的应答已经被充分确立。它们保持自身耐受性和启动针对外来和/或危险结构的保护性免疫应答的独特潜力是基于这些细胞的功能多样性和灵活性。组织DC内衬抗原门户（例如粘膜表面和皮肤）专门用于摄取广泛的化合物，包括蛋白质、脂质、碳水化合物、糖蛋白、糖脂和寡核苷酸、携带此类结构的颗粒以及凋亡或坏死细胞。该过程由具有高内吞能力的专门受体促进，这为递送设计的分子提供了潜在的靶点。然而，靶向B-和/或T细胞表位的最佳途径仍然是深入研究的主题。存在于各种组织中的未成熟DC可以被病原体、应激和炎症或修饰的代谢产物激活，这诱导细胞动员到引流淋巴结，在那里它们充当高度有效的专职抗原呈递细胞。这是由于CD 4+辅助性T淋巴细胞（Th）和CD 8+细胞毒性/细胞溶解性T淋巴细胞（Tc/CTL）能够呈递其累积的细胞内内容物。吞噬的蛋白质在细胞内被加工，并且它们的肽片段在主要组织相容性复合体编码的I类和II类分子的背景下被转运到细胞表面，以分别呈递给Th细胞和CTL。然而，DC的T细胞启动能力不仅取决于抗原呈递，而且还取决于DC的其他特征。人单核细胞来源的DC提供了一个很好的工具来研究DC在其未成熟和活化分化状态下的内化、抗原呈递和T细胞活化功能。然而，DC的这些生物学活性高度依赖于其从外周非淋巴组织到淋巴结的迁移潜力、支持DC与T淋巴细胞相互作用的粘附分子的表达以及DC分泌的细胞因子，所述细胞因子抑制对Th 1介导的细胞或Th 2介导的抗体应答的免疫应答。这些结果共同表明，单核细胞来源的DC是体外或体内靶向抗原以诱导针对病原体以及针对肿瘤的有效适应性免疫应答的有用候选物。版权所有（C）2003约翰威利父子有限公司。
responses against all classes of pathogens and also against tumors is well established. Their unique potential both to maintain self-tolerance and to initiate protective immune responses against foreign and/or dangerous structures is based on the functional diversity and flexibility of these cells. Tissue DC lining antigenic portals such as mucosal surfaces and the skin are specialized to take up a wide array of compounds including proteins, lipids, carbohydrates, glycoproteins, glycolipids and oligonucleotides, particles carrying such structures and apoptotic or necrotic cells. This process is facilitated by specialized receptors with high endocytic capacity, which provides potential targets for delivering designed molecules. The best route for targeting B- and/or T cell epitopes, however, is still the subject of intense investigation. Immature DC, which reside in various tissues, can be activated by pathogens, stress and inflammation or modified metabolic products, which induce mobilization of cells to draining lymph nodes where they act as highly potent professional antigen presenting cells. This is brought about by the ability to present their accumulated intracellular content for both CD4+ helper (Th) and CD8+ cytotoxic/cytolytic T lymphocytes (Tc/CTL). Engulfed proteins are processed intracellularly and their peptide fragments are transported to the cell surface in the context of major histocompatibility complex encoded class I and 11 molecules for presentation to Th cells and CTLs, respectively. The T cell priming capacity of DC, however, depends not only on antigen presentation but also on other features of DC.Human monocyte-derived DC provide an excellent tool to study the internalizing, antigen-presenting and T cell-activating functions of DC at their immature and activated differentiation states. These biological activities of DC, however, are highly dependent on their migratory potential from the peripheral non-lymphoid tissues to the lymph nodes, on the expression of adhesion molecules, which support the interaction of DC with T lymphocytes, and the cytokines secreted by DC, which polarize immune responses to Th1-mediated cellular or Th2-mediated antibody responses. These results altogether demonstrate that monocyte-derived DC are useful candidates for in vitro or in vivo targeting of antigens to induce efficient adaptive immune responses against pathogens and also against tumors. Copyright (C) 2003 John Wiley Sons, Ltd.