Department of Biochemistry CIIL, University of Lausanne, Épalinges, Switzerland.
Front Immunol. 2018 Aug 24;9:1912. doi: 10.3389/fimmu.2018.01912. eCollection 2018.
Dendritic cells (DCs) are the most potent antigen presenting cells and possess an incomparable ability to activate and instruct T cells, which makes them one of the cornerstones in the regulation of the cross-talk between innate and adaptive immunity. Therefore, a deep understanding of DC biology lays the foundations to describe and to harness the mechanisms that regulate the development of the adaptive response, with clear implications in a vast array of fields such as the study of autoimmune diseases and the development of new vaccines. However, the great difficulty to obtain large quantities of viable non-activated DCs for experimentation have considerably hindered the progress of DC research. Several strategies have been proposed to overcome these limitations by promoting an increase of DC abundance , by inducing DC development from DC progenitors and by generating stable DC lines. In the past years, we have described a method to derive immortalized stable DC lines, named MutuDCs, from the spleens of Mushi1 mice, a transgenic mouse strain that express the simian virus 40 Large T-oncogene in the DCs. The comparison of these DC lines with the vast variety of DC subsets described has shown that all the MutuDC lines that we have generated so far have phenotypic and functional features of type 1 conventional DCs (cDC1s). With the purpose of deriving DC lines with characteristics of type 2 conventional DCs (cDC2s), we bred a new Batf3 Mushi1 murine line in which the development of the cDC1 subset is severely defective. The new MutuDC line that we generated from Batf3 Mushi1 mice was phenotypically and functionally characterized in this work. Our results demonstrated that all the tested characteristics of this new cell line, including the expression of subset-determining transcription factors, the profile of cytokine production and the ability to present antigens, are comparable with the features of splenic CD4 cDC2s. Therefore, we concluded that our new cell line, that we named CD4 MutuDC2 line, represents a valuable model for the CD4 cDC2 subset.
树突状细胞（DCs）是最有效的抗原呈递细胞，具有无与伦比的激活和指导 T 细胞的能力，这使它们成为调节固有免疫和适应性免疫之间相互作用的基石之一。因此，深入了解 DC 生物学为描述和利用调节适应性反应发展的机制奠定了基础，这些机制在广泛的领域中具有明确的意义，如自身免疫疾病的研究和新疫苗的开发。然而，获得大量用于实验的存活非激活 DC 的巨大困难极大地阻碍了 DC 研究的进展。已经提出了几种策略来克服这些限制，例如通过促进 DC 丰度的增加、通过诱导 DC 祖细胞的发育以及通过生成稳定的 DC 系来实现。在过去的几年中，我们描述了一种从 Mushi1 小鼠脾脏中获得永生化稳定 DC 系的方法，命名为 MutuDCs，Mushi1 小鼠是一种在 DC 中表达猿猴病毒 40 大 T 抗原的转基因小鼠品系。将这些 DC 系与描述的大量各种 DC 亚群进行比较表明，我们迄今为止生成的所有 MutuDC 系都具有 1 型常规 DC（cDC1）的表型和功能特征。为了获得具有 2 型常规 DC（cDC2）特征的 DC 系，我们在 Batf3 Mushi1 小鼠中繁殖了一种新的小鼠品系，其中 cDC1 亚群的发育严重缺陷。我们从 Batf3 Mushi1 小鼠中生成的新 MutuDC 系在这项工作中进行了表型和功能特征分析。我们的结果表明，该新细胞系的所有测试特征，包括亚群决定转录因子的表达、细胞因子产生的特征和抗原呈递的能力，都与脾 CD4 cDC2 的特征相当。因此，我们得出结论，我们命名为 CD4 MutuDC2 系的新细胞系是 CD4 cDC2 亚群的一个有价值的模型。
