Schreurs M W, Eggert A A, de Boer A J, Figdor C G, Adema G J
Department of Tumor Immunology, University Hospital Nijmegen St. Radboud, Nijmegen, The Netherlands.
Eur J Immunol. 1999 Sep;29(9):2835-41. doi: 10.1002/(SICI)1521-4141(199909)29:09<2835::AID-IMMU2835>3.0.CO;2-Q.
Dendritic cells (DC) are potent antigen-presenting cells with the unique capacity to initiate primary immune responses. As a result, DC are currently used in clinical studies to induce immunity against infectious disease and malignant cells. However, multiple DC subsets exist and it has been suggested that the type of DC may affect the immune response induced. The vast majority of DC used in experimental mouse tumor models is derived from bone marrow progenitors. In contrast, most in vitro as well as in vivo human studies involve the use of DC generated from adherent peripheral blood-derived monocytes in the presence of GM-CSF and IL-4. In the current report, we describe for the first time the generation and characterization of mouse monocyte-derived DC (MODC). The results indicate that mouse MODC display similar morphology, phenotype and immunostimulatory activity as compared to bone marrow-derived DC. Both DC subsets were able to efficiently take up and subsequently cross-present protein antigen to cytotoxic T cells. Moreover, we demonstrate that vaccination with peptide-loaded MODC mediates induction of tumor-reactive immunity in vivo. The isolation and characterization of mouse MODC will provide a valuable research tool to investigate fundamental aspects of DC biology and which DC subsets are most suitable to induce anti-tumor immunity.
树突状细胞(DC)是强大的抗原呈递细胞,具有启动初次免疫反应的独特能力。因此,DC目前被用于临床研究,以诱导针对传染病和恶性细胞的免疫。然而,存在多种DC亚群,有人认为DC的类型可能会影响诱导的免疫反应。实验小鼠肿瘤模型中使用的绝大多数DC来源于骨髓祖细胞。相比之下,大多数体外和体内人体研究涉及在GM-CSF和IL-4存在的情况下,使用从贴壁外周血来源的单核细胞产生的DC。在本报告中,我们首次描述了小鼠单核细胞衍生DC(MODC)的产生和特征。结果表明,与骨髓来源的DC相比,小鼠MODC表现出相似的形态、表型和免疫刺激活性。这两种DC亚群都能够有效地摄取并随后将蛋白质抗原交叉呈递给细胞毒性T细胞。此外,我们证明用负载肽的MODC进行疫苗接种可在体内介导肿瘤反应性免疫的诱导。小鼠MODC的分离和表征将为研究DC生物学的基本方面以及哪种DC亚群最适合诱导抗肿瘤免疫提供有价值的研究工具。