Gogolák Péter, Réthi Bence, Hajas György, Rajnavölgyi Eva
Institute of Immunology, Faculty of Medicine, University of Debrecen, 98 Nagyerdei Blvd, Debrecen H-4012, Hungary.
J Mol Recognit. 2003 Sep-Oct;16(5):299-317. doi: 10.1002/jmr.650.
The cardinal role of dendritic cells (DC) in priming adaptive immunity and in orchestrating immune 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 II 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.
树突状细胞（DC）在启动适应性免疫以及协调针对各类病原体和肿瘤的免疫反应中所起的关键作用已得到充分证实。它们在维持自身耐受性以及启动针对外来和/或危险结构的保护性免疫反应方面的独特潜力，基于这些细胞的功能多样性和灵活性。位于抗原门户（如黏膜表面和皮肤）的组织DC专门摄取包括蛋白质、脂质、碳水化合物、糖蛋白、糖脂和寡核苷酸在内的多种化合物、携带此类结构的颗粒以及凋亡或坏死细胞。这一过程由具有高内吞能力的专门受体促进，这些受体为递送设计分子提供了潜在靶点。然而，靶向B细胞和/或T细胞表位的最佳途径仍是深入研究的课题。驻留在各种组织中的未成熟DC可被病原体、应激、炎症或修饰的代谢产物激活，这些物质会诱导细胞迁移至引流淋巴结，在那里它们作为高效的专职抗原呈递细胞发挥作用。这是通过将其积累的细胞内物质呈递给CD4 +辅助性（Th）和CD8 +细胞毒性/溶细胞性T淋巴细胞（Tc/CTL）的能力实现的。吞噬的蛋白质在细胞内被加工，其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至细胞表面，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，还取决于DC的其他特征。人单核细胞衍生的DC为研究DC在未成熟和活化分化状态下的内化、抗原呈递和T细胞激活功能提供了绝佳工具。然而，DC的这些生物学活性高度依赖于它们从外周非淋巴组织迁移至淋巴结的潜力、支持DC与T淋巴细胞相互作用的黏附分子的表达以及DC分泌的细胞因子，这些细胞因子使免疫反应偏向Th1介导的细胞反应或Th2介导的抗体反应。这些结果共同表明，单核细胞衍生的DC是用于体外或体内靶向抗原以诱导针对病原体和肿瘤的有效适应性免疫反应的有用候选者。
