Department of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Fundamental and Clinical Immunology," Novosibirsk, Russia.
Institute of Medicine and Psychology, Novosibirsk State University, Novosibirsk, Russia.
J Interferon Cytokine Res. 2019 Sep;39(9):531-538. doi: 10.1089/jir.2019.0031. Epub 2019 May 8.
Tolerogenic dendritic cells (tolDCs) and T-regulatory cells (Tregs) are involved in maintaining tolerance to self-antigens and foreign antigens. The cells are used as therapeutic tools for inducing tolerance to transplanted organs or tissues. We investigated the possibility of inducing Tregs in splenocyte cultures using DCs transfected with a DNA construct encoding mouse interleukin-10 (DCpIL-10). DCs were derived from bone marrow cells in the presence of rmGM-CSF and rmIL-4 and electroporated with a plasmid encoding mouse IL-10. Furthermore, DCpIL-10 was cocultured with syngeneic splenocytes. The CD4CD25FoxP3 Treg frequency, IL-10 expression, and inhibition of the mixed lymphocyte reaction were evaluated. C57Bl/6 and CBA mice differ in their initial frequency of CD4CD25FoxP3 Tregs and baseline IL-10 production. Also, the effectiveness of CD4CD25FoxP3 Treg upregulation by tolDCpIL-10 was different. In this study, DCpIL-10 from C57Bl/6 mice induced CD4CD25FoxP3 Tregs in syngenic splenocytes, which was accompanied by an increase in the IL-10 production and a decrease in the proliferation of splenocytes in response to the alloantigen. DCpIL-10 may be used to induce CD4CD25FoxP3 Tregs and the regulatory potential of splenocytes.
耐受原性树突状细胞（tolDCs）和调节性 T 细胞（Tregs）参与维持对自身抗原和外来抗原的耐受性。这些细胞被用作诱导对移植器官或组织的耐受性的治疗工具。我们研究了使用转染编码小鼠白细胞介素-10（DCpIL-10）的 DNA 构建体的 DC 来诱导脾细胞培养中的 Tregs 的可能性。DC 是在 rmGM-CSF 和 rmIL-4 的存在下从骨髓细胞中衍生而来的，并用电穿孔转染编码小鼠 IL-10 的质粒。此外，DCpIL-10 与同基因脾细胞共培养。评估 CD4CD25FoxP3 Treg 频率、IL-10 表达和混合淋巴细胞反应的抑制。C57Bl/6 和 CBA 小鼠在 CD4CD25FoxP3 Treg 的初始频率和基础 IL-10 产生方面存在差异。此外，tolDCpIL-10 上调 CD4CD25FoxP3 Treg 的有效性也不同。在这项研究中，来自 C57Bl/6 小鼠的 DCpIL-10 在同基因脾细胞中诱导了 CD4CD25FoxP3 Treg，这伴随着 IL-10 产生的增加和对同种抗原的脾细胞增殖的减少。DCpIL-10 可用于诱导 CD4CD25FoxP3 Treg 和脾细胞的调节潜力。
