Clinical Department of Neurology, Innsbruck Medical University, Austria.
Clin Immunol. 2010 Mar;134(3):296-304. doi: 10.1016/j.clim.2009.11.003. Epub 2009 Nov 28.
Macrophages and dendritic cells (DC) play an important role in the immunopathology of multiple sclerosis. We analyzed the impact of human myelin on monocyte-derived DC and describe their immunostimulatory capacity. Cells were grown on myelin and stimulated with LPS or a defined maturation cocktail. DC activation was analyzed by the expression of cell surface markers and the secretion of cytokines and chemokines. The immunostimulatory capacity of DC was assessed by allogeneic mixed-leukocyte reactions via proliferation. Additionally, their ability to bias T cells towards Th1, Th17 or Treg differentiation was investigated. We found that phagocytosis of myelin impaired the activation of DC, displayed by an impaired ability to stimulate allogeneic T cells, an increased production of TGF-beta1 and a diminished upregulation of CCR7 but did not affect the differentiation into T helper cell subsets. We hypothesize that myelin influences DC activation and plays a pivotal role in balancing immunity and tolerance.
巨噬细胞和树突状细胞（DC）在多发性硬化症的免疫病理学中发挥重要作用。我们分析了人髓鞘对单核细胞衍生的 DC 的影响，并描述了它们的免疫刺激能力。细胞在髓鞘上生长，并通过 LPS 或特定的成熟鸡尾酒进行刺激。通过细胞表面标志物的表达和细胞因子和趋化因子的分泌来分析 DC 的激活。通过增殖评估 DC 的同种异体混合白细胞反应的免疫刺激能力。此外，还研究了它们将 T 细胞偏向 Th1、Th17 或 Treg 分化的能力。我们发现，髓鞘的吞噬作用会损害 DC 的激活，表现为刺激同种异体 T 细胞的能力受损、TGF-β1 产生增加和 CCR7 的上调减少，但不会影响 T 辅助细胞亚群的分化。我们假设髓鞘会影响 DC 的激活，并在平衡免疫和耐受方面发挥关键作用。
