Monocyte-derived dendritic cells over-express CD86 in patients with systemic lupus erythematosus
Monocyte-derived dendritic cells over-express CD86 in patients with systemic lupus erythematosus
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DOI：
10.1093/rheumatology/kel061
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发表时间：
2006-09-01
期刊：
影响因子：
5.5
通讯作者：
Rammensee, Hans-Georg
中科院分区：
文献类型：
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作者：
Decker, Patrice;Koetter, Ina;Rammensee, Hans-Georg
目标.树突状细胞（Dendritic cells，DC）在调节免疫应答中起关键作用，特别是在引发初始T细胞中。最近，有人认为DC通过激活自身反应性辅助性T淋巴细胞参与系统性红斑狼疮（SLE）的发展。因此，我们比较了从狼疮患者和正常个体获得的人单核细胞衍生的DC（MDDC）的活化状态。MDDC在体外从健康供体和狼疮患者的血液中产生。通过流式细胞术分析未成熟和成熟MDDC的几种细胞表面分子。平行地，在MDDC活化之前和之后通过ELISA测定细胞因子分泌。在每次实验中，将狼疮DC与正常DC进行比较。结果。在这里，我们首次表明，狼疮MDDC自发过表达CD 86在没有任何DC激活信号相比，正常MDDC（P=0.025）。此外，与正常DC相比，具有高CD 86过表达的狼疮DC中活化诱导的IL-6分泌增加（P=0.010）。有趣的是，狼疮制剂中MDDC的百分比与疾病活动评分呈负相关（SLEDAI; P=0.031）。狼疮MDDC是预活化的，表明它们可能是更有效的抗原呈递细胞。这一结果可能部分解释了SLE外周耐受的破坏。
Objectives. Dendritic cells (DCs) play a key role in regulating immune responses, especially in priming naive T-cells. Recently, DCs have been suggested to be involved in systemic lupus erythematosus (SLE) development by activating autoreactive T-helper lymphocytes. As a consequence, we compared the activation state of human monocyte-derived DCs (MDDCs) obtained from lupus patients and normal individuals.Methods. The MDDCs were generated in vitro from blood from healthy donors and lupus patients. Immature and mature MDDCs were analysed by flow cytometry for several cell surface molecules. In parallel, cytokine secretion was determined by ELISA before and after MDDC activation. In each experiment, lupus DCs were compared with normal DCs.Results. Here, we show for the first time that lupus MDDCs spontaneously over-express CD86 in the absence of any DC activation signal as compared with normal MDDCs (P=0.025). Moreover, activation-induced IL-6 secretion was increased in lupus DCs with high CD86 over-expression as compared with normal DCs (P=0.010). Interestingly, the percentage of MDDCs in lupus preparations is negatively correlated with disease activity scores (SLEDAI; P=0.031).Conclusions. Lupus MDDCs are pre-activated suggesting that they might be more efficient antigen-presenting cells. This result might partly explain how the peripheral tolerance is broken in SLE.