Krueger T, Wohlrab U, Klucken M, Schott M, Seissler J
German Diabetes Research Institute, University of Düsseldorf, 40225, Düsseldorf, Germany.
Diabetologia. 2003 Oct;46(10):1357-65. doi: 10.1007/s00125-003-1199-0. Epub 2003 Aug 20.
AIMS/HYPOTHESIS: Dendritic cells (DCs) are professional antigen presenting cells involved in the initiation of primary immune responses and the preservation of peripheral tolerance. The aim of this study was to develop a DC vaccine for autoantigen-specific prevention of autoimmune diabetes.
Splenocytes from diabetes-prone NOD mice were cultured in conditioned media to obtain a homogeneous DC sub-population for vaccination experiments. These cells were used to modulate autoimmune responses in NOD mice after synchronization of diabetes with cyclophosphamide. After immunisation with insulin-pulsed DCs the incidence of diabetes, the insulitis grade and the cytokine production was examined.
The long-term culture of splenocytes resulted in the generation of a cell line, termed NOD-DC1, which have a phenotype of myeloid DCs (CD11c, CD11b, DEC-205), express MHC class II and co-stimulatory molecules (CD40, CD80, CD86). The NOD-DC1 cells have preserved functional activity shown by the detection of a high antigen uptake capacity, the induction of a mixed lymphocyte reaction and stimuli-dependent IL-6 and TNF-alpha secretion. Vaccination with insulin-pulsed NOD-DC1 cells results in an antigen-specific prevention of diabetes. This was mediated by a reduction of the severity of insulitis and a decrease of T helper 1 effector cells.
CONCLUSION/INTERPRETATION: We describe the generation of a DC line which confers protection from diabetes in an antigen-specific way. Our data shows that autoantigen-loaded DCs can induce strong immunoregulatory effects supporting the hypothesis that DCs are promising candidates to develop novel vaccines for the prevention of autoimmune diabetes.
目的/假设：树突状细胞（DCs）是专业的抗原呈递细胞，参与原发性免疫反应的启动和外周耐受性的维持。本研究的目的是开发一种用于自身抗原特异性预防自身免疫性糖尿病的DC疫苗。
将易患糖尿病的非肥胖糖尿病（NOD）小鼠的脾细胞在条件培养基中培养，以获得用于疫苗接种实验的同质DC亚群。在用环磷酰胺使糖尿病同步后，这些细胞被用于调节NOD小鼠的自身免疫反应。在用胰岛素脉冲DCs免疫后，检查糖尿病的发病率、胰岛炎分级和细胞因子产生情况。
脾细胞的长期培养产生了一种细胞系，称为NOD-DC1，其具有髓样DCs的表型（CD11c、CD11b、DEC-205），表达MHC II类分子和共刺激分子（CD40、CD80、CD86）。通过检测高抗原摄取能力、诱导混合淋巴细胞反应以及刺激依赖性IL-6和TNF-α分泌，表明NOD-DC1细胞保留了功能活性。用胰岛素脉冲的NOD-DC1细胞进行疫苗接种可导致抗原特异性预防糖尿病。这是通过降低胰岛炎的严重程度和减少辅助性T1效应细胞来介导的。
结论/解读：我们描述了一种以抗原特异性方式赋予糖尿病保护作用的DC系的产生。我们的数据表明，负载自身抗原的DCs可诱导强烈的免疫调节作用，支持DCs是开发预防自身免疫性糖尿病新型疫苗的有希望候选者这一假设。
